tbuckley/cabot-search huggingface dataset:
Abstract 4999: Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma
Authors: Yanxin Ren, Wei Xiong, Chun Feng, Dan Yu, Xiaoyan Wang, Qing Yang, Siting Yu, Hongjiang Zhang, Bangyun Huo, Honglu Jiang, Zuli Li, Junlin Wang, Yu-Xiong Su, Ping Yang, Yong Liao, Qi Zhong, Junwen Wang
Journal: Cancer Research (2025)

Abstract Approximately two-thirds of hypopharyngeal squamous cell carcinoma (HPSCC) are diagnosed in advanced stage, with the worst prognosis among head and neck squamous cell carcinomas (HNSCCs). Identifying biomarkers for high-risk patients who need aggressive treatment is crucial. We present mutational, transcriptomic and proteomic studies of 103 Chinese HPSCC patients, observing a higher prevalence and poorer prognosis in males comparing to females. Genes in estrogen response pathways are up-regulated and proteins phosphorylated by protein kinase C (PKC) and Cyclin-dependent kinases (CDKs) are aberrantly regulated. We identify aberrant copy number regions including SOX2 (3q26.33), FGFR (8p11.23), CCND1 (11q13.3), CDKN2A/2B (9p21.3), and MYC (8q24.21). HPV status combined with highly mutated genes as predictive markers was assessed, including SYNE1 in HPV(-), MUC4 in HPV(+) patients. We confirm the presence of four known gene expression (GE) subtypes of HNSCC in our HPSCC cohort and present the genomic alterations, patient characteristics and survival status of each subtype. A predictive model involving clinical factors and transcriptomic expression of six genes was established and cross-site validated. The findings open new opportunities for stratifying high-risk patients and molecular targets for novel therapeutic strategies. Citation Format: Yanxin Ren, Wei Xiong, Chun Feng, Dan Yu, Xiaoyan Wang, Qing Yang, Siting Yu, Hongjiang Zhang, Bangyun Huo, Honglu Jiang, Zuli Li, Junlin Wang, Yu-Xiong Su, Ping Yang, Yong Liao, Qi Zhong, Junwen Wang. Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4999.
Abstract 4959: Hearing Status and Colorectal Cancer Screening: Identifying Access Barriers
Authors: DT Bruno, Erika Bergeron, Regina Wang, Poorna Kushalnagar
Journal: Cancer Research (2025)

Background: Early detection through colorectal cancer screening is critical for effective treatment, improved survival rates, and reduced mortality. However, adherence to screening is influenced by various factors, including education and communication barriers. These barriers can be particularly pronounced for the deaf, deafblind, and hard of hearing (DDBHH) population using American Sign Language (ASL), potentially hindering preventive care. Education is widely known to be associated with cancer screening; however, the contributory role of a person’s functional ability to understand spoken language (e.g., lipreading, speechreading, combination with gestures) in a quiet room has not been explored. Methods: Using the NCI Health Information National Trends Survey in ASL as well as USPSTF guideline for colorectal cancer screening, we surveyed 566 DDBHH adult participants between July 2023 and October 2024. Binary logistic regression was used to assess the association between functional hearing ability (understand well vs cannot understand well in a quiet room) and colorectal cancer screening adherence, after adjusting for age and education. A two-sided p&amp;lt;=.05 was considered significant. Results: After adjusting for age and education, results did not indicate a significant association between functional hearing status and cancer screening adherence [β=1.14 (95% CI=0.75,1.73)], suggesting that a person's functional hearing ability does not independently influence screening rates. In this model, education level remained as a significant predictor, with lower educational attainment associated with a decreased likelihood of adhering to colorectal cancer screening guidelines [β =.51(95% CI=0.31,.84)]. Discussion: These findings highlight that functional hearing status alone is not a significant predictor of cancer screening adherence within the DDBHH community, underscoring the need for providers to look beyond a single moment of effective communication. While sign language interpreters ensure effective healthcare communication, they alone cannot address the educational disparities affecting DDBHH populations. Our study shows that DDBHH individuals with fewer years of education are less likely to undergo cancer screening. To achieve equitable health outcomes, providers should consider adding trained community health workers or patient navigators who have lived experience to the interpreter team. These navigators have potential to help overcome educational barriers and improve cancer screening rates among DDBHH patients. Citation Format: DT Bruno, Erika Bergeron, Regina Wang, Poorna Kushalnagar. Hearing Status and Colorectal Cancer Screening: Identifying Access Barriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4959.
Abstract 5035: Barcode-free demultiplexing of HiFi reads using natural genetic variation
Authors: Deniz Guney Olgun, Simai Wang, Saeid Parast, Ali Shilatifard, Hani Goodarzi, Vijay Ramani
Journal: Cancer Research (2025)

Abstract Cleverly exploiting the natural genetic variation among cells from unrelated individuals enables high throughput, highly parallel droplet single-cell RNA sequencing. We sought to lift this principle and bring analogous improvements to the setting of single-molecule long read sequencing. Toward this end, we present an error-robust method for matching individual long genomic reads to their genetic background based on a Naive Bayes Classifier. As a case study, we apply this to explore allele-specific splicing variation in the colorectal adenocarcinoma cell line DLD1 using Iso-Seq long-read RNA sequencing. Surprisingly, we uncover many allele differentially-expressed isoforms even across genes with no allele-specific expression bias in aggregate. Further, we investigate RNA-binding proteins and functional pathways potentially involved in mediating this allele-specific isoform expression pattern. In future work, our method will be applied to pooled single-molecule epigenomic screens of cancer cell line responses to treatment. Citation Format: Deniz Guney Olgun, Simai Wang, Saeid Parast, Ali Shilatifard, Hani Goodarzi, Vijay Ramani. Barcode-free demultiplexing of HiFi reads using natural genetic variation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5035.
Abstract 2581: Establishing a multi-omic spatial ECM proteome and N-glycome of pancreatic ductal adenocarcinoma tissues
Authors: Caroline G. Kittrell, Jade Macdonald, Blake Sells, Lyndsay E. Young, David DeNardo, Peggi M. Angel, Richard R. Drake
Journal: Cancer Research (2025)

Abstract Pancreatic Ductal Adenocarcinoma (PDAC), one of the leading causes of cancer related mortality nationwide, is characterized by an extensive desmoplastic stromal reaction and an altered N-glycome. Stromal collagens serve to modulate the immune microenvironment, limit nutrient and oxygen diffusion, influence chemotherapy resistance, and promote tumor progression and metastasis. Dysregulated cancer cell N-glycosylation also promotes immune evasion and neoplastic spread. Despite their important roles in cancer pathogenesis, little is known about the spatial localization and organization of the various stromal collagens, other extracellular matrix proteins, and N-glycans within the PDAC tumor microenvironment. This study utilized Matrix Assisted Laser Desorption Ionization-Mass Spectrometry Imaging (MALDI-MSI) with Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to characterize the extracellular matrix proteome and glycome of 10 primary PDAC patient tumors in collaboration with the Washington University SPORE in Pancreatic Cancer at the Siteman Cancer Center. Following PNGaseF glycosidase digestion of PDAC tissues, 214 released N-glycans and their spatial distributions were detected by MALDI-MSI. These tissues were then digested with Collagenase III for detection and localization via peptide MALDI-MSI. Tissues were scraped from the slide and further digested with Collagenase III in solution for peptide ID analysis by LC-MS/MS, with 31 identified peptides confirmed and matched to MALDI peaks. Spatially, both ECM peptides and N-glycans uniquely colocalize with various histopathologic features according to multiplex immunohistochemistry. N-glycans with bisecting N-acetylglucosamine structures associated specifically with the invasive tumor front and clusters of immune cell infiltrate, while distinct collagen species encased tumor cell regions and formed stromal nests surrounding immune cells. The degree of proline hydroxylation and other post translational modifications also varied across confirmed ECM peptides and may impact stability and deposition. From this analysis we may begin to link the N-glycome and ECM proteome of PDAC with patient survival, treatment response and other clinical variables. Citation Format: Caroline G. Kittrell, Jade Macdonald, Blake Sells, Lyndsay E. Young, David DeNardo, Peggi M. Angel, Richard R. Drake. Establishing a multi-omic spatial ECM proteome and N-glycome of pancreatic ductal adenocarcinoma tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2581.
Abstract 1275: Advancing cancer research with PDX-derived organoids: Insights into cancer stem cells and metastasis
Authors: Nicolas Ancellin, Olivier Duchamp, Didier Grillot, Kenny Herry, Nicolas Legrand, Caroline Mignard
Journal: Cancer Research (2025)

Abstract Patient-derived xenograft (PDX) organoids (PDXOs) are emerging as powerful tools for studying cancer biology and advancing therapeutic discovery. In this study, we report the generation of PDX-derived organoids from pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) PDX models, establishing a translational framework for personalized cancer research. A key focus was the detection and enrichment of cancer stem cells (CSCs) within colorectal cancer PDXOs (CR PDXOs). Through optimized culture conditions, we achieved a remarkable 30-fold enrichment of CSCs, a pivotal population driving tumor progression, therapeutic resistance, and metastasis. This enrichment highlights the utility of PDXOs in dissecting stem cell biology and targeting CSC-associated mechanisms. Using the PDAC model, we implemented tricistronic transduction to generate stable PDXOs expressing NanoLuc, mCherry, and EGFP fluorescent proteins. This genetic engineering strategy enables real-time monitoring of organoid dynamics and facilitates downstream applications, including in vivo studies. The reimplantation of these labeled PDXOs into immunocompromised mice successfully reestablished PDX tumors, demonstrating growth curves features nearly identical to those of the original PDX tumors. This PDXO-to-PDX approach underscores the fidelity of PDXOs in recapitulating patient-derived tumor biology. Further, we investigated metastatic potential using full single-cell dissociation and marker-based detection. Analysis of various tissues from mice bearing reimplanted PDAC PDXOs revealed the presence of metastatic cells in the liver, indicating the ability of PDXOs to model metastatic dissemination. This capability provides a unique platform to study metastatic mechanisms and evaluate anti-metastatic therapies. In conclusion, our study highlights the versatility and translational relevance of PDXOs in cancer research. By generating PDXOs from diverse models, enriching CSC populations, and employing advanced genetic tools for functional studies, we demonstrate the utility of PDXOs in capturing tumor complexity. The reimplantation experiments and detection of metastasis further validate PDXOs as robust systems bridging in vitro and in vivo research. This integrated approach offers critical insights into tumor biology, therapeutic responses, and metastatic behavior, paving the way for improved drug discovery and personalized treatment strategies. Citation Format: Nicolas Ancellin, Olivier Duchamp, Didier Grillot, Kenny Herry, Nicolas Legrand, Caroline Mignard. Advancing cancer research with PDX-derived organoids: Insights into cancer stem cells and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1275.
Abstract 5186: Organoids from patient-derived xenograft (PDXO) for preclinical therapeutic predictions
Authors: Chao Zhang, Xiaoying Zhuang, Lu Yin, Xiaoyi Xing, Sen Wang, Zizhuo Chen, Lei Jin, Qiangqiang Fan, Jiaping Sun, Fuyang Wang, Wenjie Gao, Qingyang Gu
Journal: Cancer Research (2025)

Tumors exhibit heterogeneity, comprising diverse cell clones, necessitating the use of preclinical models that accurately replicate clinical properties for cancer research and antitumor efficacy prediction. Patient-derived xenograft (PDX) models recapitulate key characteristics of human tumors, but are cost-intensive and time-consuming, thus unsuitable for large-scale screenings. Here, we evaluated the biological equivalence of organoid models derived from patient-derived xenograft tumors (PDXO) to PDXs. PDX organoids (PDXO) are small, organized three-dimensional structures developed from PDX tissue fragments in specialized in vitro culturing systems, enabling early-stage assessment of drugs. We have demonstrated that PDXOs are similar to their corresponding PDX counterparts in multiple aspects. Pathological staining (HE &amp; IHC) data confirmed the heterogeneity of tissue architecture, cellular composition, and microenvironment interactions inherited from PDX. Genomic analysis showed the preservation of molecular and biological characteristics. In vitro pharmacological studies demonstrated that the sensitivity of PDXOs to drugs was similar to that of the original PDX models. Furthermore, in some cases where pairs of PDXs were established from the same patient before and after targeted treatment, the corresponding PDXOs reproduced the sensitivity differences observed during in vivo studies, as well as similar mechanisms of resistance development. These clinically analogous results highlight the potential of PDXOs for preclinical and clinical drug testing, enabling more precise predictions of therapeutic outcomes. Citation Format: Chao Zhang, Xiaoying Zhuang, Lu Yin, Xiaoyi Xing, Sen Wang, Zizhuo Chen, Lei Jin, Qiangqiang Fan, Jiaping Sun, Fuyang Wang, Wenjie Gao, Qingyang Gu. Organoids from patient-derived xenograft (PDXO) for preclinical therapeutic predictions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5186.
Abstract 5424: Exploring the potential role of PGC-1β in ovarian cancer malignancy
Authors: Laura Formenti, Francesca Abramo, Giulia Dellavedova, Raffaella Giavazzi, Carmen Ghilardi
Journal: Cancer Research (2025)

Mitochondrial metabolism plays a role in tumor development and metastasis. PGC-1β is recognized as a key regulator of mitochondrial biogenesis and metabolic activity. We have recently demonstrated that PGC-1β is a biomarker of addiction to mitochondrial metabolism in ovarian cancer and determines sensitivity to OXPHOS inhibitors. Its role in cancer is largely unexplored, but some reports suggest that PGC-1β exerts pro-tumorigenic actions. We aim at unraveling the influence of PGC-1β on ovarian cancer malignancy and how it regulates ovarian cancer cell functions, besides its metabolic role. To this purpose, murine ovarian cancer cells were silenced for PGC-1β and their behavior characterized in vitro and in vivo. First, we confirmed that PGC-1β silencing caused an alteration of oxidative metabolism by Seahorse analysis, showing the reduction of oxygen consumption. Then, we found that PGC-1β depletion did not affect ovarian cancer cell proliferation in standard culture conditions, but decreased proliferation compared to control cells in starvation conditions. Moreover, PGC-1β silenced cells showed reduced invasive potential, evidenced by decreased migration and invasion, associated to diminished collagenase activity. When injected in immunocompetent mice, PGC-1β silenced cells exhibited delayed tumor growth compared to control cells. In PGC-1β silenced tumor bearing mice ascites formation, a key indicator of disease progression, was reduced compared to controls, along with decreased metastatic dissemination in the peritoneal cavity. Our data suggest that the PGC-1β depletion reduces not only cancer cell ability to survive and proliferate under nutrient limited conditions, but also their invasive potential, leading to a delay in ovarian cancer progression in vivo. Further studies are needed to elucidate the underlying molecular pathways regulated by PGC-1β. (Supported by “HEAL ITALIA” project PE_00000019 to F.A., CUP: B43D22000710006) Citation Format: Laura Formenti, Francesca Abramo, Giulia Dellavedova, Raffaella Giavazzi, Carmen Ghilardi. Exploring the potential role of PGC-1β in ovarian cancer malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5424.
Abstract 5877: Feasibility of ctDNA detection with a low-volume blood collection device
Authors: Brad Evans, Jordan Feeney, Derrick Renner, Alexey Aleshin, Matthew Rabinowitz, Steven Townson, Himanshu Sethi
Journal: Cancer Research (2025)

Abstract Patient-centric technology for personalized healthcare can transform medical research and disease management by addressing logistical hurdles, and enabling flexible, ongoing patient monitoring with reduced blood volumes. The Tasso+ low blood volume collection device allows a shift from traditional in-clinic blood collection to patient-centric, home, blood collection for volumes up to 1 mL of capillary blood. To demonstrate the utility of low blood volume collection and subsequent molecular residual disease surveillance, we evaluated the capability of the Signatera™ RUO tissue-informed assay (Natera, Inc.) to detect single nucleotide variants (SNVs) using whole blood samples collected by a microsampling device that can collect up to 500 µL, the Tasso+, as compared to traditional venipuncture. We first tested the technical feasibility of the Signatera assay to detect SNVs using a commercial circulating tumor DNA (ctDNA) reference standard (Seraseq ctDNA mutation mix v2, 0.625-5ng) spiked into low blood volumes that are representative of those obtainable from routine Tasso+ collection. Next, we tested the clinical utility of low blood volume collection using commercially obtained traditional venipuncture and Tasso+ samples from 7 cancer patients (pt) with advanced relapsed/refractory solid tumors (bladder n=1, colorectal cancer n=3, lung n=1, melanoma n=2). Venipuncture plasma samples (4 mL, 1mL, 2⨉ 500µL) and 1 in the Tasso+ device (250-500µL) were extracted per patient and assessed for ctDNA detection using the patient-informed 16-plex Signatera mPCR-NGS-based RUO ctDNA assay. The feasibility study demonstrated the ability to detect ctDNA at the single variant molecule level down to the lowest quantity of reference standard in the 250µL plasma sample. In the clinical setting, ctDNA was consistently detected among 6 of 7 pts (86%) at the 4 mL plasma volume and in 5 of 7 pts (71.4%) at all other volumes, including the 250µL volume of plasma from Tasso+ samples. The levels of ctDNA detected were generally consistent for most patients across all sample volumes, including that from the Tasso+ device. These results demonstrate that ctDNA can reliably be detected down to the single variant molecule level using the Signatera RUO assay on small plasma volumes collected with the novel Tasso+ microsampling technology. Additional evaluation using larger patient numbers would further validate this technique. Citation Format: Brad Evans, Jordan Feeney, Derrick Renner, Alexey Aleshin, Matthew Rabinowitz, Steven Townson, Himanshu Sethi. Feasibility of ctDNA detection with a low-volume blood collection device [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5877.
Abstract 5887: <i>NALCN</i> promoter methylation as a biomarker for metastatic risk in a cohort of non-small cell lung cancer patients
Authors: Eleni Thanou, Dora Londra, Ioanna Balgouranidou, Eleni Eftimiadou, Alexandra Delipetrou, Emilia Tsaroucha, Vasilis Georgoulias, Athanasios Kotsakis, Evi Lianidou, Athina N. Markou
Journal: Cancer Research (2025)

Liquid biopsy enables real-time monitoring of tumor development and response to therapy through the analysis of CTCs and ctDNA. NALCN is a sodium leak channel that is frequently involved in tumor evolution and immunity and acts as a tumor suppressor. Deletion of NALCN has been shown to increase cancer metastasis and the number of CTCs in peripheral blood. In this study, we investigated for the first time NALCN promoter methylation in (a) Aza-treated cell lines (A549, TE671, BT20, and MDA-MB-468), (b) paired NSCLC tissues (n = 22), and (c) plasma cell-free DNA (ctDNA) from patients with NSCLC (early stage n = 39, metastatic n = 39) and DNA from 10 healthy donors (HD) using a newly developed highly specific and sensitive real-time MSP method. Treatment with 5′-aza-dC induced the expression of NALCN only in the A549 cell line, suggesting that DNA methylation regulates its expression in certain cancers. The mRNA expression levels of NALCN were quantified in non-small cell lung cancer (NSCLC) and adjacent non-cancerous tissues, and it was found to be underexpressed in 54.5% of tumor tissues, with significantly higher expression in recurrence-free patients (p = 0.009) than in patients who relapsed. The NALCN methylation level was not statistically significantly correlated with the corresponding expression (p = 0.439), while Kaplan-Meier analysis showed an association between NALCN promoter hypermethylation and worse disease-free intervals (DFIs) (p = 0.017). Evaluation of NALCN methylation in ctDNA revealed that it was detected in 5.1% of early and 10.2% of advanced cases. Our results strongly suggest that epigenetic inactivation of NALCN may predict metastasis in NSCLC. Our results should be validated in further studies based on a larger patient cohort to investigate whether DNA methylation of the NALCN promoter could serve as a potential prognostic DNA methylation biomarker and predictor of metastasis in NSCLC. Citation Format: Eleni Thanou, Dora Londra, Ioanna Balgouranidou, Eleni Eftimiadou, Alexandra Delipetrou, Emilia Tsaroucha, Vasilis Georgoulias, Athanasios Kotsakis, Evi Lianidou, Athina N. Markou. NALCN promoter methylation as a biomarker for metastatic risk in a cohort of non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5887.