bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Tables from PTEN loss confers resistance to anti-PD-1 therapy in non-small cell lung cancer by increasing tumor infiltration of regulatory T cells
Authors: Exposito Francisco , Redrado Miriam , Houry Maeva , Hastings Katherine , Molero-Abraham Magdalena , Lozano Teresa , Solórzano José Luis. , Sanz-Ortega Julian , Adradas Vera , Amat Ramon , Redin Esther , Leon Sergio , Legarra Naroa , Garcia Javier , Serrano Diego , Valencia Karmele , Robles-Oteiza Camila , Foggetti Giorgia , Otegui Nerea , Felip Enriqueta , Lasarte Juan J. , Paz-Ares Luis , Zugazagoitia Jon , Politi Katerina , Montuenga Luis , Calvo Alfonso
Published: September 2024

Supplementary Tables
Supplementary Figure Legends from PTEN loss confers resistance to anti-PD-1 therapy in non-small cell lung cancer by increasing tumor infiltration of regulatory T cells
Authors: Exposito Francisco , Redrado Miriam , Houry Maeva , Hastings Katherine , Molero-Abraham Magdalena , Lozano Teresa , Solórzano José Luis. , Sanz-Ortega Julian , Adradas Vera , Amat Ramon , Redin Esther , Leon Sergio , Legarra Naroa , Garcia Javier , Serrano Diego , Valencia Karmele , Robles-Oteiza Camila , Foggetti Giorgia , Otegui Nerea , Felip Enriqueta , Lasarte Juan J. , Paz-Ares Luis , Zugazagoitia Jon , Politi Katerina , Montuenga Luis , Calvo Alfonso
Published: September 2024

Supplementary Figure Legends
Supplementary Table 1 from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

List of primers designed for Sanger sequencing across the back splicing junctions.
Supplementary Figure 1 from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

Evaluation of the most abudant circRNAs from human datasets. Boxplot showing the normalized
nCounter counts from the top 50 circRNAs extracted from publicly available human RNAseq datasets (2 normal colon, 1 tumor and paired normal adjacent tissue) (GSE77661) (A) and from the top 20 high-abundance circRNAs according to the data extracted from the three different microarray datasets comparing human tumor vs paired normal tisues (GSE126094,
GSE142837 and GSE138589) (B). C, NanoString nCounter analysis of 48 circRNA and 7 mRNA in mock and RNase R treated RNA samples from the Caco-2 cell line. Among the 48 circRNAs only 37 were expressed above cutoff levels in this cell line. D, Sanger sequencing across the backsplicing junction of the 3 circRNAs that haven't been described before. The scattered horizontal lines represent the background threshold. The box represents the interquartile range (Q1 and Q3), the median is marked with horizontral line, and whiskers represent m and maximum values.
Supplemental Materials and Methods from Targeting BCL6 in gastrointestinal stromal tumor promotes p53-mediated apoptosis to enhance the antitumor activity of imatinib
Authors: Zeng Xiangyu , Zhao Fei , Jia Jie , Ma Xianxiong , Jiang Qi , Zhang Ruizhi , Li Chengguo , Wang Tao , Liu Weizhen , Hao Yalan , Tao Kaixiong , Lou Zhenkun , Zhang Peng
Published: September 2024

Supplemental Materials and Methods
Supp. Figure 6 from Parkin deficiency suppresses antigen presentation to promote tumor immune evasion and immunotherapy resistance
Authors: Perales-Linares Renzo , Leli Nektaria Maria , Mohei Hesham , Beghi Silvia , Rivera Osvaldo D. , Kostopoulos Nektarios , Giglio Andrea , George Subin S. , Uribe-Herranz Mireia , Costabile Francesca , Pierini Stefano , Pustylnikov Sergei , Skoufos Giorgos , Barash Yoseph , Hatzigeorgiou Artemis G. , Koumenis Constantinos , Maity Amit , Lotze Michael T. , Facciabene Andrea
Published: September 2024

Figure S6
Data from Single-cell discovery and multi-omic characterization of therapeutic targets in multiple myeloma
Authors: Yao Lijun , Wang Julia T. , Jayasinghe Reyka G. , O'Neal Julie , Tsai Chia-Feng , Rettig Michael P. , Song Yizhe , Liu Ruiyang , Zhao Yanyan , Ibrahim Omar M. , Fiala Mark A. , Fortier Julie M. , Chen Siqi , Gehrs Leah , Martins Rodrigues Fernanda , Wendl Michael C. , Kohnen Danny , Shinkle Andrew , Cao Song , Foltz Steven M. , Zhou Daniel Cui , Storrs Erik , Wyczalkowski Matthew A. , Mani Smrithi , Goldsmith Scott R. , Zhu Ying , Hamilton Mark , Liu Tao , Chen Feng , Vij Ravi , Ding Li , DiPersio John F.
Published: September 2024

Abstract
Multiple myeloma (MM) is a highly refractory hematological cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which are previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA-sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA-sequencing reiterated top candidates, further affirming the ability of single cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy.
Data from Spatial positioning of immune hotspots reflects the interplay between B and T cells in lung squamous cell carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey , Jamal-Hanjani Mariam , Raza Shan E Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: September 2024

Abstract
Beyond tertiary lymphoid structures, a significant number of immune rich areas without germinal center-like structures are observed in non-small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 lung cancer patients from the TCGA. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B cell signatures. Spatial statistical analyses conducted on serial multiplex immunohistochemistry slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared to peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared to peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance towards increased intratumoral immune hotspots is indicative of a compromised anti-tumor immune response and poor outcome in lung squamous cell carcinoma.
Data from LSD1 inhibition disrupts super-enhancer driven oncogenic transcriptional programs in castration-resistant prostate cancer
Authors: Li Muqing , Liu Mingyu , Han Wanting , Wang Zifeng , Han Dong , Patalano Susan , Macoska Jill A. , Balk Steven P. , He Housheng Hansen. , Corey Eva , Gao Shuai , Cai Changmeng
Published: September 2024

Abstract
The lysine demethylase LSD1 (also called KDM1A) plays important roles in promoting multiple malignancies including both hematologic cancers and solid tumors. LSD1 targets histone and non-histone proteins and can function as a transcriptional corepressor and coactivator. LSD1 has been reported to act as a coactivator of androgen receptor (AR) in prostate cancer (PCa) and to regulate the AR cistrome via demethylation of its pioneer factor FOXA1. A deeper understanding of the key oncogenic programs targeted by LSD1 could help stratify PCa patients for treatment with LSD1 inhibitors, which are currently under clinical investigation. In this study, we performed transcriptomic profiling in an array of castration-resistant PCa (CRPC) xenograft models that are sensitive to LSD1 inhibitor treatment. Impaired tumor growth by LSD1 inhibition was attributed to significantly decreased MYC signaling, and MYC was found to be a consistent target of LSD1. Moreover, LSD1 formed a network with BRD4 and FOXA1 and was enriched at super-enhancer (SE) regions exhibiting liquid-liquid phase separation. Combining LSD1 inhibitors with BET inhibitors exhibited strong synergy in disrupting the activities of multiple drivers in CRPC, thereby inducing significant growth repression of tumors. Importantly, the combination treatment showed superior effects than either inhibitor alone in disrupting a subset of newly identified CRPC-specific SEs. These results provide mechanistic and therapeutic insights for co-targeting two key epigenetic factors and could be rapidly translated in the clinic for CRPC patients.
Data from Chi3l1 is a modulator of glioma stem cell states and a therapeutic target in glioblastoma
Authors: Guetta-Terrier Charlotte , Karambizi David , Akosman Bedia , Zepecki John P. , Chen Jia-Shu , Kamle Suchitra , Fajardo J. Eduardo , Fiser Andras , Singh Ritambhara , Toms Steven A. , Lee Chun Geun , Elias Jack A. , Tapinos Nikos
Published: September 2024

Abstract
Chi3l1 (chitinase 3-like 1) is a secreted protein that is highly expressed in glioblastoma. Here, we show that Chi3l1 alters the state of glioma stem cells (GSCs) to support tumor growth. Exposure of patient-derived GSCs to Chi3l1 reduced the frequency of CD133+SOX2+ cells and increased the CD44+Chi3l1+ cells. Chi3l1 bound to CD44 and induced phosphorylation and nuclear translocation of β-catenin, Akt and STAT3. Single cell RNA-seq and RNA velocity following incubation of GSCs with Chi3l1 showed significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq revealed that Chi3l1 increases accessibility of promoters containing a MAZ transcription factor footprint. Inhibition of MAZ downregulated a set of genes with high expression in cellular clusters that exhibit significant cell state transitions after treatment with Chi3l1, and MAZ deficiency rescued the Chi3l-induced increase of GSC self-renewal. Finally, targeting Chi3l1 in vivo with a blocking antibody inhibited tumor growth and increased the probability of survival. Overall, this work suggests that Chi3l1 interacts with CD44 on the surface of glioma stem cells to induce Akt/β-catenin signaling and MAZ transcriptional activity, which in turn upregulates CD44 expression in a pro-mesenchymal feed-forward loop. The role of Chi3l1 in regulating cellular plasticity confers a targetable vulnerability to glioblastoma.
Data from Proteomic profiling of extracellular matrix components from patient metastases identifies consistently elevated proteins for developing nanobodies that target primary tumors and metastases
Authors: Jailkhani Noor , Clauser Karl R. , Mak Howard H. , Rickelt Steffen , Tian Chenxi , Whittaker Charles A. , Tanabe Kenneth K. , Purdy Stephen R. , Carr Steven A. , Hynes Richard O.
Published: September 2024

Abstract
Metastases are hard to detect and treat, and they cause most cancer-related deaths. The relative lack of therapies targeting metastases represents a major unmet clinical need. The extracellular matrix (ECM) forms a major component of the tumor microenvironment in both primary and metastatic tumors, and certain ECM proteins can be selectively and abundantly expressed in tumors. Nanobodies against ECM proteins that show selective abundance in metastases have the potential to be used as vehicles for delivery of imaging and therapeutic cargoes. Here, we describe a strategy to develop phage-display libraries of nanobodies against ECM proteins expressed in human metastases, using as immunogens entire ECM-enriched preparations from triple-negative breast cancer (TNBC) and colorectal carcinoma (CRC) metastases to different organs as immunogens. In parallel, LC-MS/MS-based proteomics were used to define a metastasis-associated ECM signature shared by metastases from TNBC and CRC, and this conserved set of ECM proteins was selectively elevated in other tumors. As proof of concept, selective and high-affinity nanobodies were isolated against an example protein from this signature, Tenascin-C (TNC), known to be abundant in many tumor types and to play a role in metastasis. TNC was abundantly expressed in patient metastases and widely expressed across diverse metastatic sites originating from several primary tumor types. Immuno-PET/CT showed that anti-TNC nanobodies bind TNBC tumors and metastases with excellent specificity. We propose that such generic nanobodies against tumors and metastases are promising cancer-agnostic tools for delivery of therapeutics to tumor and metastatic ECM.
Data from Ubiquitin ligases Siah1a/2 control alveolar macrophage functions to limit carcinogen-induced lung adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Molinolo Alfredo , Ruppin Eytan , Murad Rabi , Ronai Ze'ev A.
Published: September 2024

Abstract
Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to therapy. Here, we characterize the function of the ubiquitin ligases Siah1a/2 in regulating the differentiation and activity of alveolar macrophages (AMs) and assess the implication of Siah1a/2 control of AMs for carcinogen-induced LUAD. Macrophage-specific genetic ablation of Siah1a/2 promoted accumulation of AMs with an immature phenotype and increased expression of pro-tumorigenic and pro-inflammatory Stat3 and β-catenin gene signatures. Administration of urethane to wild-type mice promoted enrichment of immature-like AMs and lung tumor development, which was enhanced by macrophage-specific Siah1a/2 ablation. The pro-fibrotic gene signature seen in Siah1a/2-ablated immature-like macrophages was associated with increased tumor infiltration of CD14+ myeloid cells and poorer survival of LUAD patients. Single-cell RNA-seq confirmed the presence of a cluster of immature-like AMs expressing a pro-fibrotic signature in lungs of LUAD patients, a signature enhanced in smokers. These findings identify Siah1a/2 in alveolar macrophages as gatekeepers of lung cancer development.
Data from BRCA1 Insufficiency Induces a Hypersialylated Acidic Tumor Microenvironment that Promotes Metastasis and Immunotherapy Resistance
Authors: Shu Xiaodong , Li Jianjie , Chan Un In , Su Sek Man , Shi Changxiang , Zhang Xin , An Tingting , Xu Jun , Mo Lihua , Liu Jianlin , Wang Yuqing , Li Xiaoling , Deng Min , Lei Josh Haipeng , Wang Chunfei , Tian Hao , Sun Heng , Shim Joong Sup , Zhang Xuanjun , Dai Yunlu , Yao Zhicheng , Kuang Xiaying , Lin Ying , Deng Chu-Xia , Xu Xiaoling
Published: September 2024

Abstract
Cancer metastasis is an extremely complex process affected by many factors. An acidic microenvironment can drive cancer cell migration towards blood vessels while also hampering immune cell activity. Here, we identified a mechanism mediated by sialyltransferases that induces an acidic tumor permissive microenvironment (ATPME) in BRCA1-mutant and most BRCA1-low breast cancers. Hypersialylation mediated by ST8SIA4 perturbed the mammary epithelial bilayer structure and generated an ATPME and immunosuppressive microenvironment with increased PD-L1 and PD1 expression. Mechanistically, BRCA1 deficiency increased expression of VEGF-A and IL6 to activate TGFβ-ST8SIA4 signaling. High levels of ST8SIA4 led to accumulation of polysialic acid (PSA) on mammary epithelial membranes that facilitated escape of cancer cells from immunosurveillance, promoting metastasis and resistance to αPD1 treatment. The sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac neutralized the ATPME, sensitized cancers to immune checkpoint blockade by activating CD8 T cells, and inhibited tumor growth and metastasis. Together, these findings identify a potential therapeutic option for cancers with a high level of PSA.
Data from Targeting CaMKK2 inhibits actin cytoskeletal assembly to suppress cancer metastasis
Authors: Mukherjee Debarati , Previs Rebecca A. , Haines Corinne , Al Abo Muthana , Juras Patrick K. , Strickland Kyle C. , Chakraborty Binita , Artham Sandeep , Whitaker Regina S. , Hebert Katherine , Fontenot Jake , Patierno Steven R. , Freedman Jennifer A. , Lau Frank H. , Burow Matthew E. , Chang Ching-Yi , McDonnell Donald P.
Published: September 2024

Abstract
Triple-negative breast cancers (TNBCs) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness. In validation studies, genetic disruption of CaMKK2 expression or inhibition of its activity with small molecule inhibitors disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor prognosis ovarian cancer subtype, shares many features with TNBC, and CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Mechanistically, CaMKK2 increased the expression of the phosphodiesterase PDE1A which hydrolyzed cyclic guanosine monophosphate (cGMP) to decrease the cGMP-dependent activity of protein kinase G1 (PKG1). Inhibition of PKG1 resulted in decreased phosphorylation of vasodilator stimulated phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate cell movement. Together, these findings establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis by impacting the actin cytoskeleton. Further, it identifies CaMKK2 as a potential therapeutic target that can be exploited to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC.
Data from Pre-existing immunity drives the response to neoadjuvant chemotherapy in esophageal adenocarcinoma
Authors: Arbore Giuseppina , Albarello Luca , Bucci Gabriele , Punta Marco , Cossu Andrea , Fanti Lorella , Maurizio Aurora , Di Mauro Francesco , Bilello Vito , Arrigoni Gianluigi , Bonfiglio Silvia , Biancolini Donatella , Puccetti Francesco , Elmore Ugo , Vago Luca , Cascinu Stefano , Tonon Giovanni , Rosati Riccardo , Casorati Giulia , Dellabona Paolo
Published: September 2024

Abstract
Current treatment for patients with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy (nCT), alone or combined with radiotherapy, before surgery. However, fewer than 30% of treated patients show a pathological complete response to nCT, which correlates with increased 5-year survival compared to non-responders. Understanding the mechanisms of response to nCT is pivotal to better stratify patients and inform more efficacious therapies. Here, we investigated the immune mechanisms involved in nCT response by multi-dimensional profiling of pre-treatment tumor biopsies and blood from 68 EAC patients (34 prospectively and 34 retrospectively collected), comparing complete responders versus non-responders to nCT. At the tumor level, complete response to nCT was associated with molecular signatures of immune response and proliferation, increased putative anti-tumor tissue-resident memory CD39+CD103+CD8+ T cells and reduced immunosuppressive T regulatory cells and M2-like macrophages. Systemically, complete responders showed higher frequencies of immunostimulatory CD14+CD11c+HLA-DRhigh cells and reduced PDL1+ monocytic myeloid-derived suppressor cells, along with high plasma GM-CSF (pro-inflammatory) and low IL-4, CXCL10, C3a, and C5a (suppressive). Plasma pro-inflammatory and suppressive cytokines correlated directly and inversely, respectively, with the frequency of tumor-infiltrating CD39+CD103+CD8+ T cells. These results suggest that pre-existing immunity in baseline tumors drives the clinical activity of nCT in locally advanced EAC. Furthermore, it may be possible to stratify patients based on predictive immune signatures, enabling tailored neoadjuvant and/or adjuvant regimens.
Data from ESRRB inhibits the TGF-β signaling pathway to drive cell proliferation in cervical cancer
Authors: Li Qin-Shu , Zheng Peng-Sheng
Published: September 2024

Abstract
Estrogen-related receptor β (ESRRB) is a member of the orphan nuclear receptor family and mediates stem cell self-renewal and early embryonic development. Previous studies have also reported that ESRRB plays a role in development and progression of breast cancer and prostate cancer. In this study, we observed that ESRRB was highly expressed in cervical cancer (CC) and was associated with disease progression. Knocking out ESRRB using CRISPR/Cas9 gene editing in cervical cancer cells induced cell cycle arrest at the transition from the G0/G1 phase to the S phase, resulting in inhibition of cell proliferation in vitro and reduced tumor growth in vivo. Conversely, ectopic expression of ESRRB significantly promoted the proliferation of cervical cancer cells. ESRRB activated transcription of SMAD7, a TGF-β pathway inhibitor, which blocked phosphorylation and nuclear translocation of SMAD2/3 to the nucleus, thereby downregulating CDKN1A and upregulating CCNA2 and MYC. In turn, MYC transactivated ESRRB and upregulated SMAD7, thus forming a positive feedback loop with ESRRB. Together, these findings identify the tumor promoting function of ESRRB in cervical cancer and reveal a mechanism by which ESRRB stimulates cell proliferation to promote cancer progression.
Data from Endocrine therapy synergizes with SMAC mimetics to potentiate antigen presentation and tumor regression in hormone receptor-positive breast cancer
Authors: Hermida-Prado Francisco , Xie Yingtian , Sherman Shira , Nagy Zsuzsanna , Russo Douglas , Akhshi Tara , Chu Zhengtao , Feit Avery , Campisi Marco , Chen Minyue , Nardone Agostina , Guarducci Cristina , Lim Klothilda , Font-Tello Alba , Lee Irene , García-Pedrero Juana , Canadas Israel , Agudo Judith , Huang Ying , Sella Tal , Jin Qingchun , Tayob Nabihah , Mittendorf Elizabeth A. , Tolaney Sara M. , Qiu Xintao , Long Henry , Symmans William F. , Lin Jia-Ren , Santagata Sandro , Bedrosian Isabelle , Yardley Denise A. , Mayer Ingrid A. , Richardson Edward T. , Oliveira Giacomo , Wu Catherine J. , Schuster Eugene F. , Dowsett Mitch , Welm Alana L. , Barbie David , Metzger Otto , Jeselsohn Rinath
Published: September 2024

Abstract
Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics analysis of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated B2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of ET on cancer cells were explored, which revealed that ET plays a crucial role in facilitating the chromatin binding of RelA, a key component of the NF-κB complex. Consequently, heightened NF-κB signaling enhanced the response to interferon-gamma, leading to the upregulation of β2-microglobulin and other antigen presentation-related genes. Further, modulation of NF-κB signaling using a SMAC-mimetic in conjunction with ET augmented T-cell migration and enhanced MHC-I specific T-cell mediated cytotoxicity. Remarkably, the combination of ET and SMAC-mimetics, which also block pro-survival effects of NF-κB signaling through the degradation of inhibitors of apoptosis (IAP) proteins, elicited tumor regression through cell-autonomous mechanisms, providing additional support for their combined use in HR+ breast cancer.
Data from Galectin-1 mediates chronic STING activation in tumors to promote metastasis through MDSC recruitment
Authors: Nambiar Dhanya K. , Viswanathan Vignesh , Cao Hongbin , Zhang Weiruo , Guan Li , Chamoli Manish , Holmes Brittany , Kong Christina , Hildebrand Rachel , Koong Amanda Jeanette. , von Eyben Rie , Plevritis Sylvia , Li Lingyin , Giaccia Amato , Engleman Edgar , Le Quynh-Thu
Published: September 2024

Abstract
The immune system plays a crucial role in the regulation of metastasis. Tumor cells systemically change immune functions to facilitate metastatic progression. Through this study, we deciphered how tumoral Galectin-1 (Gal1) expression shapes the systemic immune environment to promote metastasis in head and neck cancer (HNC). In multiple preclinical models of HNC and lung cancer in immunogenic mice, Gal1 fostered the establishment of a pre-metastatic niche through polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which altered the local microenvironment to support metastatic spread. RNA sequencing of MDSCs from pre-metastatic lungs in these models demonstrated the role of PMN-MDSCs in collagen and extracellular matrix remodeling in the pre-metastatic compartment. Gal1 promoted MDSC accumulation in the pre-metastatic niche through the NF-κB signaling axis, triggering enhanced CXCL2-mediated MDSC migration. Mechanistically, Gal1 sustained NF-κB activation in tumor cells by enhancing STING protein stability, leading to prolonged inflammation-driven MDSC expansion. These findings suggest an unexpected pro-tumoral role of STING activation in metastatic progression and establish Gal1 as an endogenous positive regulator of STING in advanced-stage cancers.
Data from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

Abstract
Circular RNAs (circRNAs) are covalently closed molecules that can play important roles in cancer development and progression. Hundreds of differentially expressed circRNAs between tumors and adjacent normal tissues have been identified in studies using RNA-sequencing or microarrays, emphasizing a strong translational potential. Most previous studies have been performed using RNA from bulk tissues and lack information on the spatial expression patterns of circRNAs. Here, we showed that the majority of differentially expressed circRNAs from bulk tissue analyses of colon tumors relative to adjacent normal tissues were surprisingly not differentially expressed when comparing cancer cells directly with normal epithelial cells. Manipulating the proliferation rates of cells grown in culture revealed that these discrepancies were explained by circRNAs accumulating to high levels in quiescent muscle cells due to their high stability; on the contrary, circRNAs were diluted to low levels in the fast-proliferating cancer cells due to their slow biogenesis rates. Thus, different sub-compartments of colon tumors and adjacent normal tissues exhibited striking changes in circRNA expression patterns. Likewise, the high circRNA content in muscle cells was also a strong confounding factor in bulk analyses of circRNAs in bladder and prostate cancer. Together, these findings emphasize the limitations of using bulk tissues for studying differential circRNA expression in cancer and highlight a particular need for spatial analysis in this field of research.
Data from Asparagine Dependency Is a Targetable Metabolic Vulnerability in TP53-Altered Castration-Resistant Prostate Cancer
Authors: Yoo Young A. , Quan Songhua , Yang William , Guo Qianyu , Rodríguez Yara , Chalmers Zachary R. , Dufficy Mary F. , Lackie Barbara , Sagar Vinay , Unno Kenji , Truica Mihai I. , Chandel Navdeep S. , Abdulkadir Sarki A.
Published: September 2024

Abstract
TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we have shown here that TP53-altered prostate cancer exhibits an increased dependency on asparagine (Asn) and overexpresses Asn synthetase (ASNS), the enzyme catalyzing the synthesis of Asn. Mechanistically, the loss or mutation of TP53 transcriptionally activated ASNS expression, directly and via mTORC1-mediated ATF4 induction, driving de novo Asn biosynthesis to support CRPC growth. TP53-altered CRPC cells were sensitive to Asn restriction by knockdown of ASNS or L-asparaginase treatment to deplete the intracellular and extracellular sources of Asn, respectively, and cell viability was rescued by Asn addition. Notably, pharmacological inhibition of intracellular Asn biosynthesis using a glutaminase inhibitor and depletion of extracellular Asn with L-asparaginase significantly reduced Asn production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for targeting Asn production to treat these lethal prostate cancers.

Significance: TP53-mutated castration-resistant prostate cancer is dependent on asparagine biosynthesis due to upregulation of ASNS and can be therapeutically targeted by approaches that deplete intracellular and extracellular asparagine.
Supplementary Table 5 from Somatic mosaic chromosomal alterations and death of cardiovascular disease causes among cancer survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: September 2024

Supplementary Table 5: Cox regression analyses evaluating the effect of mosaic chromosomal alterations on the risk of death of cardiovascular disease causes, coronary artery disease causes, from cancer, and any cause of death stratified by smoking status groups
Supplementary Table 16 from Somatic mosaic chromosomal alterations and death of cardiovascular disease causes among cancer survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: September 2024

Supplementary Table 16: Cox regression analyses for the effect of mosaic chromosomal alterations on the risk of incident cardiovascular endpoints aged ≥65 years old (n=15,273)
Supplementary Table 14 from Somatic mosaic chromosomal alterations and death of cardiovascular disease causes among cancer survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: September 2024

Supplementary Table 14: Cox regression analyses of the effect of mosaic chromosomal alterations on the risk of death from cancer according to cancer type
Supplemental Table 6 from Nitrated polycyclic aromatic hydrocarbon (nitro-PAH) signatures and somatic mutations in diesel exhaust-exposed bladder tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella
Published: September 2024

Ever diesel and nitro-PAH signatures adjusted for smoking
Table S5 from Exploring the complex relationship between gut microbiota and risk of colorectal neoplasia using bidirectional Mendelian Randomization analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: September 2024

Table S5 shows the SNPs for adenoma and polyps.
Table S1 from Exploring the complex relationship between gut microbiota and risk of colorectal neoplasia using bidirectional Mendelian Randomization analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: September 2024

Table S1 shows the SNPs that associated with 24 microbiota taxa in MiBioGen (P<5×10-8).
Supplementary Table S3 from The Association of Neighborhood Characteristics and Frailty in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study
Authors: Schwartz Lindsay F. , Dhaduk Rikeenkumar , Howell Carrie R. , Brinkman Tara M. , Ehrhardt Matthew J. , Delaney Angela , Srivastava Deo Kumar , Lanctot Jennifer Q. , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. , Henderson Tara O.
Published: September 2024

Supplementary Table S3 shows comparisons of pre-frailty/frailty odds between weighted and unweighted models, completed to evaluate for potential participation bias
Supplementary Table S7 from Associations of post-diagnosis lifestyle with prognosis in women with invasive breast cancer
Authors: Troeschel Alyssa N. , Hartman Terryl J. , McCullough Lauren E. , Ergas Isaac J. , Collin Lindsay J. , Kwan Marilyn L. , Ambrosone Christine B. , Flanders W Dana , Bradshaw Patrick T. , Cespedes Feliciano Elizabeth M. , Roh Janise M. , Wang Ying , Valice Emily , Kushi Lawrence H.
Published: September 2024

Subdistribution hazard ratios (sdHR) and 95% confidence intervals (95% CI) for the association of 2-year post-diagnosis lifestyle with breast cancer-specific mortality (n=1,736) and breast cancer recurrence (n=1,705).
Supplementary Table S11 from Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies
Authors: Liu Zhiqiang , Zhang Yingfan , Lagergren Jesper , Li Shanshan , Li Jingru , Zhou Zhixian , Hu Zhijian , Xie Shao-Hua
Published: September 2024

Supplementary Table S11 shows statistically significant associations between prediagnostic circulating levels of sex hormone and the risk of gastrointestinal cancer NOT included in meta-analysis.
Figure S3 from Incidence trends and survival in early-onset esophagogastric adenocarcinoma: A Swedish population-based cohort study
Authors: Radkiewicz Cecilia , Asplund Johannes , Lagergren Jesper
Published: September 2024

Early- (age 20-54 years, solid) and later-onset (age 55-99 years, dashed line) esophagogastric adenocarcinoma excess mortality rate (EMR) per 1,000 person-years over 5 years from diagnosis.
Supplementary Table 15 from Hepatocellular Carcinoma Surveillance Among Individuals with Cirrhosis: Trends by Payer, Etiology and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018
Authors: Hsu Christine D. , Henderson Louise M. , Jackson Bradford E. , Baggett Christopher D. , Jonsson Funk Michele , Olshan Andrew F. , Gupta Parul , Barritt A Sidney. , Sanoff Hanna K. , Wheeler Stephanie B. , Moon Andrew M. , Lund Jennifer L.
Published: September 2024

Supplementary Table 15 includes one-year cumulative incidences for HCC surveillance overall and by insurance type, by calendar year of cirrhosis diagnosis, without imputing deaths for individuals insured through private insurance (% and 95% confidence intervals).
Supplementary Table 1 from Folate intake and ovarian cancer risk among women with endometriosis: a case-control study from the Ovarian Cancer Association Consortium
Authors: Gersekowski Kate , Ibiebele Torukiri I. , Doherty Jennifer A. , Harris Holly R. , Goodman Marc T. , Terry Kathryn L. , Wu Anna H. , Bandera Elisa V. , Qin Bo , Ong Jue-Sheng , Tyrer Jonathan P. , Dixon-Suen Suzanne C. , Modugno Francesmary , Risch Harvey A. , Webb Penelope M.
Published: September 2024

Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Supplementary Figure 1 from Folate intake and ovarian cancer risk among women with endometriosis: a case-control study from the Ovarian Cancer Association Consortium
Authors: Gersekowski Kate , Ibiebele Torukiri I. , Doherty Jennifer A. , Harris Holly R. , Goodman Marc T. , Terry Kathryn L. , Wu Anna H. , Bandera Elisa V. , Qin Bo , Ong Jue-Sheng , Tyrer Jonathan P. , Dixon-Suen Suzanne C. , Modugno Francesmary , Risch Harvey A. , Webb Penelope M.
Published: September 2024

Supplementary Figure 1 shows a flowchart of exclusions to obtain the study population, with the number of cases and controls eligible for the analysis.
Supplementary Table S2 from Pre-diagnostic 25-hydroxyvitamin D in association with cancer specific- and all-cause mortality among low income, non-Hispanic Black Americans with colorectal cancer
Authors: Lawler Thomas P. , Khankari Nikhil K. , Shu Xiao-Ou , Steinwandel Mark , Cai Qiuyin , Jurutka Peter W. , Zheng Wei , Warren Andersen Shaneda
Published: September 2024

Supplementary Table S2: Median [IQR] time between SCCS enrollment and cancer incidence, end of follow-up in 218 colorectal cancer patients
Table ST1 from A review of the application of spatial survival methods in cancer research: trends, modelling and visualization techniques
Authors: Bizuayehu Habtamu Mellie , Cameron Jessica K. , Dasgupta Paramita , Baade Peter D.
Published: September 2024

Supplementary Table S1 shows search terms and keywords
Supplementary Figure S3 from Development of a breast cancer risk prediction model incorporating polygenic risk scores and non-genetic risk factors for Korean women
Authors: Choi Jihye , Ha Tae-woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: September 2024

Estimation of absolute risk of breast cancer by seven percentiles for women at different ages estimated using data from HEXA 1st. The absolute risk of developing breast cancer predicted by the multiple PRS model (PRS38_ASN+PRS190_EB). The dotted lines represent the average risks. (A) Lifetime absolute risk (B) 5-year absolute risk
Supplementary Table S1 from Urine pH and Risk of Bladder Cancer in Northern New England
Authors: Fischer Alexander H. , Wong Jason YY. , Baris Dalsu , Koutros Stella , Karagas Margaret R. , Schwenn Molly , Johnson Alison , Alguacil Juan , Silverman Debra T. , Rothman Nathaniel
Published: September 2024

Supplementary Table S1 shows urine pH and risk of bladder cancer among ever-smokers.
Supplementary Table S1 from Characteristics of Cancer Epidemiology Studies that Employ Metabolomics: A Scoping Review
Authors: Yu Catherine T. , Farhat Zeinab , Livinski Alicia A. , Loftfield Erikka , Zanetti Krista A.
Published: September 2024

Supplementary Table S1 shows metabolite super-pathways examined in semi-targeted population-based cancer metabolomics studies.
Supplementary Table 3 from Patterns of evidence-based care for the diagnosis, staging, and first-line treatment of breast cancer by race-ethnicity: a SEER-Medicare study
Authors: Herbach Emma L. , Nash Sarah H. , Lizarraga Ingrid M. , Carnahan Ryan M. , Wang Kai , Ogilvie Amy C. , Curran Michaela , Charlton Mary E.
Published: September 2024

Supplementary Table 3 shows adjusted rate ratios for all applicable outcomes stratified by age at diagnosis.
Supplemental Table 4 from Germline mutations in 12 genes and risk of ovarian cancer in three population-based cohorts
Authors: Kotsopoulos Joanne , Hathaway Cassandra A. , Narod Steven A. , Teras Lauren R. , Patel Alpa V. , Hu Chunling , Yadav Siddhartha , Couch Fergus J. , Tworoger Shelley S.
Published: September 2024

Supplemental Table 4: Mutation frequencies in high grade serous, endometroid, or poorly differentiated ovarian cancer cases and controls and risk of ovarian cancer in the NHS, NHSII, and CPSII
Figure S1 from A Genomic Analysis of Esophageal Squamous Cell Carcinoma in Eastern Africa
Authors: Van Loon Katherine , Mmbaga Elia J. , Mushi Beatrice P. , Selekwa Msiba , Mwanga Ally , Akoko Larry Onyango. , Mwaiselage Julius , Mosha Innocent , Ng Dianna L. , Wu Wei , Silverstein Jordyn , Mulima Gift , Kaimila Bongani , Gopal Satish , Snell Jeff M. , Benz Stephen C. , Vaske Charles , Sanborn Zack , Sedgewick Andrew J. , Radenbaugh Amie , Newton Yulia , Collisson Eric A.
Published: September 2024

Supplementary Figure S1. Measurement of RNA Quantity and Quality using PAXgene tissue container vs. RNAlater.
Supplementary Table 1 from Changes in geographic variation and socioeconomic inequalities in esophageal cancer mortality in China, 1973-2017
Authors: Ran Xianhui , Zheng Rongshou , Zeng Hongmei , Zhang Siwei , Sun Kexin , Han Bingfeng , Wang Shaoming , Chen Ru , Li Li , Wei Wenqiang , He Jie
Published: September 2024

Supplementary Table 1 shows three major measures of data quality of cancer registries included in this study.
Table S3 from Dietary fish and n-3 polyunsaturated fatty acid consumption, and renal cell carcinoma risk in Japan: The Japan Public Health Center-based Prospective Study
Authors: Takahashi Michiko , Sobue Tomotaka , Zha Ling , Kitamura Tetsuhisa , Iwasaki Motoki , Inoue Manami , Yamaji Taiki , Tsugane Shoichiro , Sawada Norie
Published: September 2024

Supplementary Table S3. Risk of RCC based on the energy-adjusted dietary intakes of various fish categories.
Supplementary Table S1 from Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations
Authors: Trendowski Matthew R. , Lusk Christine M. , Wenzlaff Angela S. , Neslund-Dudas Christine , Gadgeel Shirish M. , Soubani Ayman O. , Schwartz Ann G.
Published: September 2024

This supplementary table includes the SNPs previously identified in Hung et al. (2021) that were used in the development of our polygenic risk score in non-Hispanic White and African American participants.
Data from Using DEPendency of association on the number of Top Hits (DEPTH) as a complementary tool to identify novel colorectal cancer susceptibility loci.
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , Maclnnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: September 2024

Abstract
Background: DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome.

Methods: We conducted a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer (CRC) data from the Colon Cancer Family Registry (CCFR) (5,735 cases and 3,688 controls), and GECCO (8,865 cases and 10,285 controls) studies. A DEPTH score >1 was used to identify candidate susceptibility regions common to both studies. We compared DEPTH results against those from conventional GWAS analyses of these two studies as well as against 132 published susceptibility regions.

Results: Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous CRC GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the HLA locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data.

Conclusions: DEPTH can identify candidate susceptibility regions for CRC not identified using conventional analyses of larger datasets.

Impact: DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.
Data from Body Composition, Relative Dose Intensity, and Adverse Events Among Patients with Colon Cancer
Authors: Cheng En , Caan Bette J. , Cawthon Peggy M. , Evans William J. , Hellerstein Marc K. , Shankaran Mahalakshmi , Nyangau Edna , Campbell Kristin L. , Lee Catherine , Binder Alexandra M. , Meyerhardt Jeffrey A. , Schmitz Kathryn H. , Cespedes Feliciano Elizabeth M.
Published: September 2024

Abstract
Background: Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events.

Methods: We estimated 1) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); 2) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and 3) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures.

Results: Higher CT SMA and DXA ALM were significantly associated with lower risk of reduced RDI (odds ratios: 0.56 [0.38, 0.81] for CT SMA; 0.56 [0.37, 0.84] for DXA ALM). No measurements of muscle or adipose tissue were associated with adverse events.

Conclusions: More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events.

Impact: Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.