bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3110: In depth comparison of cell free DNA blood collection tubes
Authors: Desharnais Joel , Vasquez Jacob M. , Reshatoff Katya J. , Bui Quyen , Chen Han-Mei , Tsvetanova Billyana , Lu Jerry , Murray Amber N. , Costa Gina L. 
Published: September 2020

Abstract
Liquid biopsy continues to gain traction as a minimally invasive method to monitor biomarkers associated with malignancy and metastasis such as cell-free DNA (cfDNA). However, cell-free DNAs are present in low quantities and are prone to rapid degradation and contamination, which presents challenges for the detection of rare cfDNA targets. Higher molecular weight genomic DNA from poorly stabilized leukocytes can also serve to contaminate plasma, compromising liquid biopsy assay results by increasing the total amount of extracted DNA while diluting rare cfDNA targets; leading to sample rejection or false negative results. Efficient and robust preservation of cfDNA and prevention of leukocyte lysis is thus essential for the accuracy of downstream tests, and several blood collection tubes (BCTs) designed to stabilize cfDNA are now commercially available.
The work presented here evaluates LBgard® Blood Tubes (Biomatrica), the Streck Cell-Free DNA BCTs® (Streck), and PAXgene Blood ccfDNA Tubes (PreAnalytix) for analysis of cfDNA. Healthy donor blood was collected into collection tubes, and the samples were either stored for several days at a range of temperatures or subjected to various shipping conditions. Several metrics were evaluated, including hemolysis, plasma recovery, cfDNA preservation, contamination with genomic DNA (gDNA), and quantitation of cfDNA targets. Differences were observed between the various tubes evaluated, especially when tested under real-world stress shipping conditions. Data reports performance metrics and evaluations across the multiple formulations of BCTs and highlights the criticality of collection tube selection in biomarker investigation and study.
Citation Format: Joel Desharnais, Jacob M. Vasquez, Katya J. Reshatoff, Quyen Bui, Han-Mei Chen, Billyana Tsvetanova, Jerry Lu, Amber N. Murray, Gina L. Costa. In depth comparison of cell free DNA blood collection tubes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3110.
Abstract 3148: FOXC1 expression is associated with a triple-negative basal-like phenotype in breast cancer
Authors: Cho William C. , Ma Victor W. , Cheuk Wah , So Grace Y. , Chin Rebecca Y. 
Published: September 2020

Abstract
Introduction: Triple-negative breast carcinoma (TNBC) is a group of aggressive tumors that are resistant to hormonal therapy. Forkhead box C1 (FOXC1) has been shown to play a crucial role in cancer pathogenesis by cancer stem cell regulation, epithelial to mesenchymal transition and tumor progression in basal-like breast cancer (BLBC). This study examined the expression of FOXC1 in basal-like TNBC, which may potential be exploited as a treatment target for this group of tumors.
Materials and Methods: Immunohistochemical Peroxidase-DAB system and Opal immunofluorescence staining system were employed to detect FOXC1 and cytokeratin 14 (CK14) expressions in 44 formalin-fixed paraffin-embedded (FFPE) invasive ductal breast carcinoma (IDC) and 150 IDC samples on tissue microarray. CK14 was used to identify the BLBC subtype. The staining was scored semi-quantitatively according to the intensity with a mean score from 0-4.
Results: CK14 identified 15 (34%) BLBC in the FFPE tissues and 24 (16%) BLBC in the samples on tissue microarray. Of the 44 FFPE tissues, FOXC1 expression was observed in 100% of the BLBC and 83% of TNBC, while it was only found in 15% of non-TNBC. The mean staining intensity of FOXC1 was lower in non-TNBC (0.30) compared to TNBC (2.16) and basal-like TNBC (2.60). These findings were confirmed in the tissue microarray, which also revealed a strong positive correlation of FOXC1 with basal-like TNBC. In addition, our results showed that FOXC1 was more frequently expressed in ER-negative (22%), PR-negative (21%) and HER2-negative (19%) breast cancers than in ER-positive (3%), PR-positive (3%) and HER2-positive (5%) breast cancers. Moreover, FOXC1 expression was significantly associated with high tumor grade (p = 0.000041) and high tumor-infiltrating lymphocytes (TILs) (p = 0.000001).
Conclusion: FOXC1 is highly expressed in TNBC, particularly among the basal-like subgroup, as opposed to other breast cancers. It accurately classifies the BLBC subtype which may be used as a surrogate marker for this molecular subtype. We find that FOXC1 has an inverse correlation with ER, PR and HER2, as well as a positive correlation with tumor grade and TILs. Our finding suggests that FOXC1 may serve as a potential treatment target for basal-like TNBC.
Citation Format: William C. Cho, Victor W. Ma, Wah Cheuk, Grace Y. So, Rebecca Y. Chin. FOXC1 expression is associated with a triple-negative basal-like phenotype in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3148.
Abstract 3149: An assay quantifying pro-peptides of type XI collagen (PRO-C11) in serum provides novel insight into the pathology of non-small cell lung cancer (NSCLC)
Authors: Willumsen Nicholas , Kehlet Stephanie N. , Jensen Tina M. , Nissen Neel I. , Karsdal Morten A. 
Published: September 2020

Abstract
Background: The tumor microenvironment (TME) is characterized by an extensive number and activity of cancer-associated fibroblasts (CAFs). CAFs are the most abundant cell type in the TME of stroma-rich tumors and dictate patient outcome. One of the most specific CAF genes is COL11A1 which encodes the α1-chain of type XI collagen. Type XI collagen is synthesized as a pro-collagen and proteolytically cleaved by bone-morphogenetic protein 1 (BMP-1) to yield mature type XI collagen. Cleaved pro-peptides released to the circulation could serve as biomarkers of type XI collagen formation and provide novel insight into patients with cancer. We developed and evaluated an assay targeting the N-terminal pro-peptide of type XI collagen for quantifying this specific fragment in the circulation (serum) of patients with non-small cell lung cancer (NSCLC).
Methods: A monoclonal antibody was raised against the C-terminal neo-epitope on the N-terminal pro-peptide of type XI collagen and employed in the development of a competitive ELISA (PRO-C11). PRO-C11 was measured in serum from 40 stage 3+4 NSCLC patients and compared to 32 age-matched healthy controls. PRO-C11 was correlated with demographic and clinical characteristics (age, BMI, smoking, metastasis, histological subtype).
Results: The PRO-C11 assay is technically robust with specificity only for the BMP-1 generated type XI collagen pro-peptide neo-epitope. PRO-C11 was significantly elevated in NSCLC compared to age-matched healthy controls (p&lt;0.0001). No correlation (Pearson, p&gt;0.05) was seen between PRO-C11 and age, BMI, smoking status, metastasis (y/n) and histological subtype (squamous cell carcinoma vs. adenocarcinoma).
Conclusion: The present study validates a new serological assay quantifying the pro-peptide of type XI collagen. The biomarker has promising potential for NSCLC and warrants further investigations into stroma-rich cancers. Further studies are needed to evaluate the diagnostic/prognostic use of PRO-C11 in NSCLC.
Citation Format: Nicholas Willumsen, Stephanie N. Kehlet, Tina M. Jensen, Neel I. Nissen, Morten A. Karsdal. An assay quantifying pro-peptides of type XI collagen (PRO-C11) in serum provides novel insight into the pathology of non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3149.
Abstract 3155: Interferon-gamma-induced melanoma plasticity and response to PD-1 blockade therapy
Authors: Kim Yeon Joo , Sheu Katherine M. , Tsoi Jennifer , Abril-Rodriguez Gabriel , Grasso Catherine , Hoffmann Alexander , Smale Stephen T. , Graeber Thomas G. , Puig-Saus Cristina , Ribas Antoni 
Published: September 2020

Abstract
Melanoma is a cancer of melanocytes, which develop from neural crest cells during embryogenesis. One of the ways melanoma can resist targeted therapy or adoptive T cell transfer therapy (ACT) is by dedifferentiation, whereby the tumor becomes less melanocytic and more neural crest-like. ACT-induced dedifferentiation and therapy resistance was a result of tumor necrosis factor (TNF) from antitumor T cells (Landsberg, Nature 2012), which can serve as a positive control for inflammatory cytokine-induced melanoma plasticity.
To study whether immune checkpoint blockade induces melanoma dedifferentiation, we analyzed RNA-seq data from paired biopsies of 68 patients before and during anti-PD-1 therapy. Surprisingly, the tumors of patients with complete or partial response dedifferentiate following therapy (paired p= 0.00015), but those of stable or progressive disease do not (paired p= 0.31 and 0.32, respectively). As the presence of interferon-gamma signatures in biopsies is best correlated with response to anti-PD-1 therapy, we hypothesized that interferon-gamma mediates dedifferentiation.
We dedifferentiated four human melanoma cell lines by in vitro exposure to long-term (three to five weeks) interferon-gamma and compared it to three days of TNF as positive control. Although TNF and long-term interferon-gamma induced similar phenotypic changes based on flow cytometry, ATAC-seq showed that they each drive different global chromatin remodeling. Motif enrichment analyses revealed STAT6, TFAP2C, and SOX proteins are key transcription factors involved in interferon-gamma-induced dedifferentiation. Inferred protein activity analysis of the matching RNA-seq data showed that these regulators, as well as IRF3 and HMGA1, alter in activity selectively with dedifferentiation.
In conclusion, dedifferentiation may be a marker of positive response to anti-PD-1 therapy, mediated by chronic exposure to T cells producing interferon-gamma.
Citation Format: Yeon Joo Kim, Katherine M. Sheu, Jennifer Tsoi, Gabriel Abril-Rodriguez, Catherine Grasso, Alexander Hoffmann, Stephen T. Smale, Thomas G. Graeber, Cristina Puig-Saus, Antoni Ribas. Interferon-gamma-induced melanoma plasticity and response to PD-1 blockade therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3155.
Abstract 3162: Early change in peripheral blood CD4+T cells associated with the clinical outcome in gastrointestinal cancer patients receiving immune checkpoint inhibitors
Authors: Lu Zhi-Hao , Liu Chang , Wang Yan-ni , Li Shuang , Jiao Xi , Zou Jian-ling , Wang Zheng-hang , Qi Chang-song , Zhang Xiao-tian , Li Jian , Shen Lin 
Published: September 2020

Abstract
Purpose: Predictive biomarkers for immune checkpoint inhibitors (ICIs) are urgently needed in advanced gastrointestinal (GI) carcinoma.
Methods: Peripheral blood lymphocyte, lymphocyte subset and early dynamic changes of them were retrospectively analyzed in patients with GI cancer treated with ICIs. Cox regression and Kaplan-Meier analyses were conducted to analyze survival.
Results: Eighty patients were enrolled. According to whether tumor progression occurred by 6 months after the initial ICI, patients were divided into two cohorts, 6m-progressive disease (PD) (N=40) and 6m-non-PD (nPD) (N=40).BaselineCD4+/CD8+ T cell (CD4/CD8) ratio was higher in the 6m-nPD cohort than in the 6m-PD cohort. Lymphocyte subsets were obtained both at baseline and before the second dose of ICIs in 61 patients. In total, 54.1% (33/61) of patients experienced tumor progression within 6 months of the initial ICI treatment, and these patients showed significant declines in CD4+ T cell counts (CD4-C1-decline) (p=0.0002) and the CD8+ T cell counts (CD8-C1-decline) (p=0.045) after the first dose of ICIs. In multivariate analyses, CD4-C1-decline (HR=12.66; 95% CI: 2.17-73.91; p=0.005) was an independent prognostic factor for OS. Furthermore, Stratified analyses indicated that CD4-C1-decline was a poor prognostic factor for tumor progression in patients with a deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H).
Conclusion: Early change in CD4+ T cell counts in peripheral blood samples may help as prognostic biomarkers for GI cancer patients treated with ICIs. Further prospective studies are needed to validate this conclusion.
Citation Format: Zhi-Hao Lu, Chang Liu, Yan-ni Wang, Shuang Li, Xi Jiao, Jian-ling Zou, Zheng-hang Wang, Chang-song Qi, Xiao-tian Zhang, Jian Li, Lin Shen. Early change in peripheral blood CD4+T cells associated with the clinical outcome in gastrointestinal cancer patients receiving immune checkpoint inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3162.
Abstract 3167: Immune checkpoint inhibition re-challenge after a planned treatment interruption in patients with pancreatic adenocarcinoma with mismatch repair deficient tumors
Authors: Florou Vaia , Nevala-Plagemann Chris , Barber Kristin , Mastroianni Jenna , Cavaliery Courtney Christine , Garrido-Laguna Ignacio 
Published: September 2020

Abstract
Background: Immune checkpoint inhibitors (CPI) are used in numerous solid cancers as well as hematologic malignancies. The optimal duration of immunotherapy to maintain durable responses has not been defined, neither is the efficacy of CPI when the disease progresses during a planned treatment interruption. Pembrolizumab has been approved for all mismatch repair deficient tumors regardless of histology, based on cumulative data of five clinical trials including multiple solid tumors. Only eight patients with pancreatic cancer were included in those trials used for CPI approval in this setting. Outside of this, there is currently no role for standard of care CPI in pancreatic cancer.
Methods: We screened all patients with pancreatic adenocarcinoma treated at our institution and identified two patients who had mismatch repair deficient tumors and received immune checkpoint inhibitors.
Results: Two patients with metastatic pancreatic cancer were retreated with an anti- PD-1 antibody after a planned treatment interruption which, did not occur in the context of disease progression or development of immune-related adverse events. Both patients were initially treated for more than one year (17 and 22 months each) with partial response of their disease, before therapy was discontinued after at least six months of stable radiographic findings were achieved. One patient had disease progression after ten months off therapy and the other 16 months after treatment discontinuation. Both were treated with the same checkpoint inhibitor upon progression and had radiographic regression of their disease within two months after treatment initiation. Both remain on CPI with continuing radiographic and clinical response.
Conclusions: CPI re-challenge may be an efficient therapy when discontinued after maximal response has been achieved. Only twelve cases have been described in the literature where patients were retreated with CPI upon progression of disease while off therapy. Our case series contributes to that body of literature and is the first to describe patients with pancreatic cancer re-challenged with CPI. Mismatch repair deficient pancreatic cancers are rare, but CPI have similar efficacy compared to other tumors with similar molecular features.
Citation Format: Vaia Florou, Chris Nevala-Plagemann, Kristin Barber, Jenna Mastroianni, Courtney Christine Cavaliery, Ignacio Garrido-Laguna. Immune checkpoint inhibition re-challenge after a planned treatment interruption in patients with pancreatic adenocarcinoma with mismatch repair deficient tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3167.
Abstract 317: Organoid and TIL co-culture system models the human tumor immune microenvironment and drug sensitivity
Authors: Tokumaru Yoshihisa , Oshi Masanori , Katsuta Eriko , Matsuhashi Nobuhisa , Futamura Manabu , Yoshida Kazuhiro , Takabe Kazuaki 
Published: September 2020

Abstract
BACKGROUNDS: Host tumor immune microenvironment has been shown to play a critical role on the outcome of the breast cancer patient. Among the immune cells, tumor infiltrating lymphocytes (TILs) were shown to be a predictive biomarker for the efficacy of chemotherapy by clinical trials. Triple negative breast cancer (TNBC) is known to have high infiltration of TILs compared with other subtypes. TILs were reported to be associated with the response to doxorubicin and cyclophosphamide, and with better survival in breast cancer patients. Recently, there are accumulating evidences that organoids generated from patient tumors are useful as models for drug sensitivity pre-clinical trials. Here, we hypothesized that co-culture of TILs with organoids will mimic human tumor immune microenvironment and enhance the drug sensitivity.
MATERIAL AND METHODS: GSE22226 that contains both clinical data and gene expression profile of untreated tumors was used as the breast cancer patient cohort that underwent neoadjuvant chemotherapy (NAC). Relative fractions of 22 types of infiltrating immune cells were estimated from tumor gene expression with the CIBERSORT method. Organoids of the same tumors grown as mouse xenografts were generated using standard methods. Organoids (1000/well of 96-w plate) were treated with doxorubicin (0.01-100 µM) for 2 days before addition of TILs of same patient (1-16 x103 per well). Cytotoxicity was assessed after another two days with the CellTiter-Glo 3D cell viability assay.
RESULTS: We first assessed the clinical relevance of TILs in response outcome of NAC by utilizing the previously reported cohort, in which Adriamycin, Cyclophosphamide and Taxane were used. We found that the number of TILs were significantly higher in the patients that achieved pathological complete response (pCR) when compared with the ones that did not. We established 18 PDX models all of which are from TNBC and we successfully expanded TILS 7 of these patients. We derived 8 organoids from the patients. We performed the experiment of adding TILs to the organoids. TILs effectively killed organoids when TILs were cultured at 1:8 or 1:16 ratio. Furthermore, the killing of organoids by doxorubicin was enhanced by the addition of TILs.
CONCLUSION: Amount of TILs associated with better outcome in NAC cohort. In pre-clinical setting, addition of TIL intensified the sensitivity of organoids to doxorubicin.
Citation Format: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe. Organoid and TIL co-culture system models the human tumor immune microenvironment and drug sensitivity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 317.
Abstract 3205: classifieRc: An interactive web interface for the molecular classification of colorectal cancer from RNA-sequencing data
Authors: Quinn Gerard , Sessler Tamas , Allen Wendy , Maguire Sarah , Dunne Philip , McArt Darragh , VanSteenhouse Harper , Gallagher Peter , Lees Andrea , Longley Dan , Seligmann Bruce , Wappett Mark , McDade Simon 
Published: September 2020

Abstract
Background: Transcriptional predictors are increasingly important for sub-typing cancer patients and understanding disease aetiology, predicting patient outcomes and response to treatment. Colorectal cancers (CRC) can be classified by transcriptionally inferred consensus (CMS) and intrinsic (CRIS) sub-types, annotating transcriptional profiles derived from colorectal cancer samples with these sub-types and other transcriptionally inferred predictors requires an experienced bioinformatician and is time-consuming.
Methods: Publically available R packages CMSclassifier, CRISclassifier, MCP-counter and DoRothEA have been integrated into a web interface using the R/Shiny framework which allows users to upload gene expression data which can be additionally normalized with DESeq2. Visualization of this data can be interacted with through using plotly.
Results: To address this bottleneck, we developed the classifieRC Shiny app, which enables rapid analysis, annotation of colorectal cancer transcriptional profiles with state-of-the-art transcriptional CRC sub-typing (CMS and CRIS) as well as estimation of cellular composition (MCP-Counter) and transcription factor activity predictions (DoRothEA). classifieRC can be accessed through a web-based interface, a locally deployable R-script or executable software, with capability of publishing datasets and their resulting analysis to Shiny.IO.
Conclusions: classifieRc enables researchers to rapidly annotate colorectal transcriptomic datasets with molecular sub-types and of functional predictions without the need for a dedicated bioinformatician, expediting insights related patient cohort analyses and novel discoveries. classifieRc provides an easy to use flexible framework for functional annotation transcriptomic datasets and a platform for development of other disease specific apps.
Citation Format: Gerard Quinn, Tamas Sessler, Wendy Allen, Sarah Maguire, Philip Dunne, Darragh McArt, Harper VanSteenhouse, Peter Gallagher, Andrea Lees, Dan Longley, Bruce Seligmann, Mark Wappett, Simon McDade. classifieRc: An interactive web interface for the molecular classification of colorectal cancer from RNA-sequencing data [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3205.