tbuckley/cabot-search huggingface dataset:
Abstract 3264: Digital profiling of tumor-derived extracellular vesicle RNA: a novel approach for early diagnosis and monitoring of pancreatic cancer patients
Authors: Hyojin Um, Taewon Son, Yeochan Kim, Elizabeth Maria Clarissa, Hanna Kim, Jihye Ahn, Juhee Park, Beomhee Ahn Ahn, Kyusang Lee, Beomseok Lee, Yoon-Kyoung Cho
Journal: Cancer Research (2025)

Abstract Introduction: Pancreatic cancer remains a leading cause of cancer-related deaths due to challenges in early diagnosis and the lack of effective biomarkers. Current diagnostic methods are insufficient, necessitating novel approaches. This study explores the use of extracellular vesicle RNA (EV-RNA) from plasma as a diagnostic tool, leveraging a new assay that facilitates membrane fusion between EVs and liposomes. Methods: The study introduces a digital EV-RNA profiling assay (LiquiDyne) that uses charge-mediated fusion between extracellular vesicles and charged liposomes (CLIPs) carrying molecular beacons. This process occurs on a droplet microfluidic chip, where the surface charge of CLIPs is adjusted to optimize fusion efficiency. The assay was validated analytically using EVs from pancreatic cancer cell lines (MIA-PaCa-2, PANC-1, PSN-1, Capan-2) with known KRAS mutations (G12C, G12D, G12R, G12V). Clinical validation involved testing retrospective patient samples across all stages of pancreatic cancer. Results: The assay requires only 20 µL of plasma, removing the need for prior EV isolation or RNA preparation and thus minimizing sample loss. It successfully detected KRAS mutations in both cell lines and patient samples with high accuracy, demonstrating its potential as a reliable diagnostic tool. Conclusions: This innovative assay offers a promising method for early pancreatic cancer diagnosis by enabling precise quantification of rare EV subpopulations. It holds potential not only for diagnosis but also for monitoring minimal residual disease, thus addressing critical gaps in current pancreatic cancer diagnostics. Citation Format: Hyojin Um, Taewon Son, Yeochan Kim, Elizabeth Maria Clarissa, Hanna Kim, Jihye Ahn, Juhee Park, Beomhee Ahn Ahn, Kyusang Lee, Beomseok Lee, Yoon-Kyoung Cho. Digital profiling of tumor-derived extracellular vesicle RNA: a novel approach for early diagnosis and monitoring of pancreatic 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 3264.
Abstract 7139: An optimized extraction and library preparation workflow for sensitive mutation detection in clinical cfDNA samples
Authors: Lauren P. Saunders, James Erickson, Margaret R. Heider, Jian Sun, Adrian Reich, Ben Lepene
Journal: Cancer Research (2025)

Abstract Monitoring cell-free DNA (cfDNA) - small DNA fragments circulating in the bloodstream - provides valuable insights into various tissues throughout the body and diverse health conditions. cfDNA has been particularly useful in tracking cancer progression, although its low abundance can lead to low mutation copy frequencies, especially in early-stage cancers where limited tumor presence yields minimal cfDNA in circulation. Optimizing molecular biology techniques for maximal cfDNA recovery and purity as well as high NGS library conversion efficiency is essential to improve detection of low-frequency cancer mutations. In this study, several cfDNA next generation sequencing (NGS) library preparation workflows were evaluated for sensitivity and workflow efficiency. The NEBNext UltraExpress DNA library prep kit is a new, fast library prep that has not yet been optimized for cfDNA analysis. We compared it with the NEBNext Ultra II DNA Library Prep Kit, which performs well with cfDNA. Both kits were evaluated downstream of the NEAT Liquid Biopsy kit, which is optimized for gDNA removal using Nanotrap Particle technology and results in a highly concentrated DNA elution. With the ability to concentrate down to 20 µL, this extraction kit pairs well with the NEBNext UltraExpress DNA kit which has a 15 µL input. This allows more of the sample to be analyzed, leading to higher detection of low frequency alleles. Initial workflow assessments were analyzed with mutation spike-ins of 0-5% allele frequency in healthy plasma, then confirmed with clinical samples containing known mutations. All workflows produced high complexity libraries with high quality data and successfully detected spike-in mutations, with expected variant allele frequencies. Mutations were also successfully detected in clinical plasma samples demonstrating the essential need for efficient extraction and library prep methods. Citation Format: Lauren P. Saunders, James Erickson, Margaret R. Heider, Jian Sun, Adrian Reich, Ben Lepene. An optimized extraction and library preparation workflow for sensitive mutation detection in clinical cfDNA samples [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 7139.
Abstract 6220: Disparities in cancer incidence among African American and non-Hispanic white participants in the Agricultural Health Study and North Carolina residents
Authors: Somayina C. Ezennia, Christine G. Parks, Laura E. Beane Freeman, Anne Taylor, Gabriella Andreotti, Stella Koutros, Dale P. Sanders, Jonathan N. Hofmann
Journal: Cancer Research (2025)

Abstract Disparities in cancer incidence between African American (AA) and non-Hispanic white (NHW) populations in the U.S. are well documented. However, no studies have examined cancer incidence disparities in farming populations. Given unique occupational hazards (e.g., pesticides, zoonotic diseases, diesel exhaust), we hypothesized that racial disparities in cancer incidence may be more pronounced among AA farmers than in the general population. We investigated cancer incidence among North Carolina (NC) participants in Agricultural Health Study (AHS), a prospective cohort of pesticide applicators and their spouses enrolled between 1993-1997. This investigation included 28, 579 participants (1, 511 AA, 27, 068 NHW), identifying 6, 511 cancer cases (432 AA, 6, 079 NHW) through 2021. We calculated standardized incidence ratios (SIRs), standardized incidence rate estimates (SREs) and 95% confidence intervals (CI) for overall and site-specific cancers in the AHS relative to the general population in NC.Overall, the SIR was higher for AA in the AHS (SIR = 1.19, CI 1.08 - 1.31) than for AA in NC (SIR = 1.05, CI 1.04 - 1.05), with notably high SIRs for certain sites like prostate cancer, multiple myeloma, and colorectal cancer (Table 1). For prostate cancer and multiple myeloma, we observed the lowest incidence among NHW in the general population and the highest in AA in the AHS cohort. Our findings of greater disparities in cancer incidence among AA in the AHS compared with AA in the general population may be related to differences in certain agricultural exposures or economic and social barriers faced by AA farmers; we plan to further investigate these factors in future efforts. These findings and ongoing efforts are needed to help promote the health and well-being of AA farmers. Citation Format: Somayina C. Ezennia, Christine G. Parks, Laura E. Beane Freeman, Anne Taylor, Gabriella Andreotti, Stella Koutros, Dale P. Sanders, Jonathan N. Hofmann. Disparities in cancer incidence among African American and non-Hispanic white participants in the Agricultural Health Study and North Carolina residents [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 6220.
Abstract 5137: Epithelial-to-mesenchymal transition coordinates REEP2 to drive pro-metastatic membrane trafficking program in lung cancer
Authors: Kevin Fulp, Oluwafunminiyi Obaleye, Guan-Yu Xiao
Journal: Cancer Research (2025)

Abstract Membrane trafficking governs the transport of molecules to both intracellular and extracellular locations, thereby maintaining cell homeostasis. During cancer progression, alterations in membrane trafficking are frequently observed. Nevertheless, no effective drugs target membrane trafficking currently and the many mechanisms underlying the dysregulation of membrane trafficking in cancer progression remain a significant unresolved question. Our recent research discovered that the epithelial-to-mesenchymal transition (EMT) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression in the tumor microenvironment (TME) in lung adenocarcinoma (LUAD). Importantly, blocking the EMT-driven membrane trafficking program re-sensitizes LUAD to immune checkpoint inhibition, suggesting significant therapeutic potential for this pathway. To dissect the pro-metastatic membrane trafficking program, we initiated a CRISPRi in vivo screen to assess more than 2, 000 trafficking-related genes in syngeneic mouse LUAD models for their requirements for tumorigenesis. Our preliminary studies identified REEP2 as a novel regulator of the EMT-dependent membrane trafficking program, which is linked to poor prognosis and an immunosuppressive TME in LUAD patients. Our findings here show that the EMT-activating transcription factor ZEB1 upregulates REEP2 by relieving its silencing mediated by miR-193a, thereby facilitating endoplasmic reticulum (ER) polarization to the Golgi apparatus. The REEP2-driven ER polarization promotes pro-metastatic secretory trafficking. Blockade of REEP2 suppresses LUAD cell proliferation, migration, invasion in vitro, and tumor metastasis in the syngeneic LUAD mouse tumor model. Our findings elucidate the molecular mechanisms underlying LUAD metastasis and support the development of REEP2 inhibitors to prevent EMT-driven cancer metastasis. Citation Format: Kevin Fulp, Oluwafunminiyi Obaleye, Guan-Yu Xiao. Epithelial-to-mesenchymal transition coordinates REEP2 to drive pro-metastatic membrane trafficking program in lung cancer [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 5137.
Abstract 3067: The long non-coding RNA CDH3-AS1 facilitates gemcitabine resistance and lung metastasis via TGFβ activation in pancreatic ductal adenocarcinoma
Authors: Mengli Yang, Rui Wang, Haijian Sun, Ming Dong, Qiang Chen
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with chemotherapy serving as the primary treatment for PDAC when surgery is not feasible. Gemcitabine is commonly used as the first-line chemotherapeutic agent in PDAC treatment, yet resistance to gemcitabine frequently emerges, necessitating the development of novel strategies to improve its efficacy. In our study, we established a gemcitabine resistant PDAC cell model through an evolutionary process involving gradually increasing gemcitabine concentrations. RNA-Seq analysis revealed significant upregulation of extracellular matrix (ECM) signaling in resistant cells. ECM dysregulation impeded gemcitabine uptake, leading to resistance. In addition, resistant cells showed reduced proliferation compared to parental cells, further exacerbating resistance. Mechanically, we found enhanced activation of the transforming growth factor β (TGFβ) pathway in resistant cells, resulting in increased expression of ECM-related genes and cyclin kinase Inhibitor p57. Moreover, we found that the long non-coding RNA (LncRNA) CDH3-AS1, the antisense of CDH3, was significantly upregulated in resistant cells and exhibited a positive correlation with ECM signaling in SMAD4 mutant PDAC, suggesting its role as a regulator of TGFβ signaling. Disrupting CDH3-AS1 impaired TGFβ activation in resistant cells by inhibiting TGFBR1 and SMAD4, thereby reversing gemcitabine resistance. Interestingly, CDH3-AS1 also regulated the expression of CDH3 in resistant cells, promoting lung metastasis through mediating epithelial-to-mesenchymal transition (EMT). The study reveals CDH3-AS1 as a novel regulator of TGFβ activation that contributes to PDAC progression, providing a new potential therapeutic target for the treatment of this aggressive cancer. Citation Format: Mengli Yang, Rui Wang, Haijian Sun, Ming Dong, Qiang Chen. The long non-coding RNA CDH3-AS1 facilitates gemcitabine resistance and lung metastasis via TGFβ activation in pancreatic ductal adenocarcinoma [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 3067.
Abstract 7083: Classical and basal like cells in donor tissues reveal phenotypic heterogeneity of pancreatic intraepithelial neoplasia
Authors: Jude O. Okoye, Rosina Carr, Ahmed M. Elhossiny, Alberto C. Olivei, Imade Williams, Lei Sun, Yaqing Zhang, Eileen S. Carpenter, Timothy L. Frankel, Marina Pasca Di Magliano
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that affects individuals of all ages, with marginal improvements in patient survival rates over the years despite available treatments. Although Pancreatic Intraepithelial Neoplasia (PanIN), an early lesion, is known to precede PDAC, identifying individuals at risk of developing PDAC remains a challenge for clinicians. Recent studies have demonstrated both inter- and intra-heterogeneity of PDAC, as well as the aggressive nature of its phenotypes, but little is known about the heterogeneity of PanIN and its risk of progression in humans. To address this gap, we investigated transplant-incompetent samples from 89 male and female White and African-American patients, ages 21 to 76 years, collected through the Gift of Life program. Pathologic analyses using basic histological techniques revealed an average burden of three PanINs per 2 cm x 2 cm of donor tissue. Single-cell RNA sequencing and protein validation identified distinct classical and basal-like cells, along with expression of cytokines that correlate to the phenotypes previously reported in PDAC. In some patients, subpopulations within the already-established aggressive basal cells were identified. Regardless of cell phenotype, the senescence state of most of the identified PanINs may explain why these patients were not diagnosed with PDAC during their lifetimes. Given that most PDAC develop from PanIN and PanINs are often found adjacent to tumors, we are currently probing upregulated and downregulated pathways in tumor-associated PanINs and donor PanINs with tumor-like features, as well as crosstalk between classical and basal PanINs and their microenvironments. We are also developing a model to provide further insight into the risk of disease progression using spatial transcriptomic analysis. This knowledge could lead to more effective methods for early detection and treatment of the lethal disease. Citation Format: Jude O. Okoye, Rosina Carr, Ahmed M. Elhossiny, Alberto C. Olivei, Imade Williams, Lei Sun, Yaqing Zhang, Eileen S. Carpenter, Timothy L. Frankel, Marina Pasca Di Magliano. Classical and basal like cells in donor tissues reveal phenotypic heterogeneity of pancreatic intraepithelial neoplasia [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 7083.
Abstract 6607: Leveraging somatic mutations to distinguish tumor/normal cells in scRNA-seq datasets across different cancer types
Authors: Cindy Kim, Eke Snoeren, Francesc Muyas, Natasha Markuzon
Journal: Cancer Research (2025)

Recent advancements in single-cell RNA sequencing (scRNA-seq) have significantly impacted clinical oncology. However, the accurate interpretation of scRNA-seq data remains challenging due to the limitations of current methodologies in distinguishing between different cell types within a tissue sample. Despite substantial efforts to construct comprehensive cell atlases, differentiating malignant from non-malignant cells is still a time-consuming process. Current approaches primarily rely on marker genes, gene expression signatures, and copy number alterations (CNAs), though these methods are not universally applicable to all cancer types. In our study, we explored the potential of leveraging somatic mutations to differentiate tumor and normal cells within scRNA-seq datasets from ovarian and colorectal cancer samples. We conducted a comparative analysis of the effectiveness of CNAs and single nucleotide variants (SNVs), as well as developed a supervised machine learning (ML) method leveraging their combination for improved prediction. The findings highlighted the importance of understanding the biological mechanisms underlying mutational processes for accurate tumor cell detection. Specifically, tumor cells in ovarian cancer samples exhibited a higher prevalence of CNAs, whereas colorectal cancer samples, particularly those with mismatch repair deficiency (MMRd), showed limited utility of CNAs for predicting tumor/normal cell status. In contrast, SNVs proved to be extremely valuable in identifying highly mutated tumor cells in colorectal cancer, with tumor mutational burden (TMB) serving as one of the highly effective predictors. In conclusion, our study utilizes a previously developed framework for detecting somatic mutations in scRNA-seq data for the robust and effective identification of tumor cells and their clusters in tissue samples. This framework is cancer-type agnostic and could help improve tumor cell detection in cancers with a high prevalence of CNAs. Citation Format: Cindy Kim, Eke Snoeren, Francesc Muyas, Natasha Markuzon. Leveraging somatic mutations to distinguish tumor/normal cells in scRNA-seq datasets across different cancer types [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 6607.
Abstract 6718: Analysis of the pathological significance of CD109 in pancreatic cancer using the mouse model
Authors: Yoshiki Murakumo, Yasutaka Sakurai, Masaaki Ichinoe
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high fatality rate. Because there are few effective treatments for advanced pancreatic cancer, the development of new molecular targeted therapies is desired. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. We recently reported that positive expression of CD109 in tumor cells was significantly associated with poor prognosis in PDAC. In addition, CD109 expression was also detected in the stroma surrounding the tumor cells, suggesting its expression in cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC. In the present study, we aimed to further investigate the histopathological and prognostic significance of CD109 in PDAC using the mouse model. In the normal mouse pancreas, CD109 expression was almost undetectable by X-gal staining and in situ hybridization. In the PDAC tissues, CD109 expression was detected not only in the tumor cells but also in the surrounding stromal cells, which was similar to that in human PDAC. CD109 expression was predominantly detected in undifferentiated tumor cells rather than differentiated tumor cells. In addition, we generated a CD109-deficient PDAC mouse model line, KPC-CD109KO, and it was revealed that CD109-deficinet KPC mice tended to develop differentiated adenocarcinomas compared with KPC mice with wild-type CD109. However, CD109 deficiency did not affect the survival of KPC mouse. Taken together, CD109 is expressed not only in the tumor cells but also in the stroma in PDAC, and is associated with tumor differentiation in PDAC. Citation Format: Yoshiki Murakumo, Yasutaka Sakurai, Masaaki Ichinoe. Analysis of the pathological significance of CD109 in pancreatic cancer using the mouse model [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 6718.
Abstract 6729: The role of L-MYC in prostate cancer
Authors: Jeyaluxmy Sivalingam, Xiuping Yu
Journal: Cancer Research (2025)

Abstract The MYC family of transcription factors, comprising MYC, N-MYC, and L-MYC, regulates essential cellular processes, including proliferation, metabolism, differentiation, and apoptosis. While MYC and N-MYC have been extensively studied in prostate cancer (PCa), the role of L-MYC remains underexplored. To investigate the expression patterns of these MYC family genes across different stages of PCa, we analyzed publicly available mRNA expression data from normal prostate tissues, adenocarcinoma prostate cancer (AdPCa), neuroendocrine prostate cancer (NEPCa), and PCa cell lines representing AdPCa, castration-resistant prostate cancer (CRPCa), and NEPCa (H660). Our analysis revealed elevated MYC expression in AdPCa patients and AdPCa/CRPCa cell lines, whereas N-MYC showed no significant expression across PCa stages. In contrast, L-MYC was prominently expressed in NEPCa patients and the NEPCa cell line H660. RNA-seq data from patient biopsies (PMID: 26855148) further confirmed increased L-MYC levels in CRPCa-NE compared to CRPCa-Adeno. Additionally, neuroendocrine markers (NCAM1, INSM1, ASCL1, and NEUROD1) were co-expressed with L-MYC in NEPCa, underscoring its association with neuroendocrine differentiation. The expression of L-MYC in H660 cells was further validated by RT-qPCR and Western blot. Despite their shared genomic structure and high sequence homology, MYC family genes exhibit mutually exclusive expression patterns in PCa. Transcription factor binding site (TFBS) analysis revealed unique regulatory elements that may contribute to this differential expression, warranting further investigation. Ongoing RNA-seq analysis of L-MYC knockdown in H660 cells aims to identify pathways regulated by L-MYC and provide insights into its potential as a therapeutic target in NEPCa. These findings suggest that L-MYC plays a pivotal role in NEPCa progression and highlight the importance of understanding the regulatory mechanisms driving its unique expression. Citation Format: Jeyaluxmy Sivalingam, Xiuping Yu. The role of L-MYC in prostate cancer [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 6729.