tbuckley/cabot-search huggingface dataset:
Abstract 6226: Chinese visceral adiposity index outperforms other obesity indexes in association with increased overall cancer incidence: Findings from prospective MJ cohort study
Authors: Mengying Wang, Chi Pang Wen, David Ta-Wei Chu, Huakang Tu, Wenyuan Li, Xifeng Wu
Journal: Cancer Research (2025)

Abstract Background: Chinese Visceral Adiposity Index (CVAI) is an integrated index to measure visceral adiposity tissue (VAT). This study is to assess the relationship between VAT indices such as CVAI, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP) waist circumference (WC) and waist-hip ratio (WHR) with overall and specific cancer incidence in Chinese. Methods: 332, 297 individuals from the MJ cohort were tracked from 1996 to 2007. We utilized multivariable Cox proportional hazards models to examine the connections of five baseline visceral obesity indices and cancer incidence. Results: A robust dose-response correlation between CVAI and the risk of overall cancer incidence was observed. The HRs were 1.45 (95% CI: 1.2-1.76) and 2.03 (95% CI: 1.52-2.72) for males and females when comparing Quintile 5 to the reference. The HRs for WC were 1.27 (95% CI: 1.08-1.49) among males and 1.19 (95% CI: 1.01-1.40) among females, and WHR showed significance in males (HR:1.28; 95% CI: 1.13-1.45), LAP showed significance in females (HR: 1.25; 95% CI: 1.04-1.5). VAI was not related to overall cancer incidence. Conclusion: The results support CVAI's practicality as a superior clinical marker for predicting cancer incidence in the Chinese population compared to traditional central obesity indices. Citation Format: Mengying Wang, Chi Pang Wen, David Ta-Wei Chu, Huakang Tu, Wenyuan Li, Xifeng Wu. Chinese visceral adiposity index outperforms other obesity indexes in association with increased overall cancer incidence: Findings from prospective MJ cohort study [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 6226.
Abstract 6305: hGRN-ChEAR: human transcription factor regulatory network with a knowledge graph interactive user interface
Authors: Anna I. Byrd, John Erol Evangelista, Alexander Lachmann, Ho-Young Chung, Sherry L. Jenkins, Avi Ma'ayan
Journal: Cancer Research (2025)

Abstract Gene expression is controlled by transcription factors that selectively bind to DNA to regulate mRNA expression of all human genes. In cancer, gene expression regulation is misconfigured to accelerate uncontrolled cell proliferation. Transcription factors control the expression of other transcription factors, forming a complex gene regulatory network (GRN) with switches, feedback loops, and other regulatory motifs. Many experimental methods and computational tools have been developed to reconstruct GRNs in-silico. Here we present a novel approach to reconstruct the human GRN. By submitting thousands of gene sets from the RummaGEO resource for transcription factor enrichment analysis with ChEA3, we are able to distill a signed and directed edges that connect all human transcription factors to construct a novel human GRN. The GRN has 130, 793 signed and directed edges between 703 source and 1, 543 target nodes. The network is made accessible via an interactive web-based application called the Human Gene Regulatory Network based on ChEA3 and RummaGEO (hGRN-ChEAR). hGRN-ChEAR enables users to query the GRN by searching for single or pairs of transcription factors, as well as by submitting their gene sets to perform transcription factor enrichment analysis. To demonstrate the utility of hGRN-ChEAR, we systematically identified transcription factor subnetworks that regulate differentially expressed genes in tumors from ten cancer types, and 69 subtypes, profiled by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). hGRN-ChEAR is freely available from: https://hgrn-chear.maayanlab.cloud/. Citation Format: Anna I. Byrd, John Erol Evangelista, Alexander Lachmann, Ho-Young Chung, Sherry L. Jenkins, Avi Ma'ayan. hGRN-ChEAR: human transcription factor regulatory network with a knowledge graph interactive user interface [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 6305.
Abstract 5479: Development of novel luminescent assays for sensitive and specific quantitation of double-stranded RNA in mRNA vaccines
Authors: Rich Moravec, Jun Wang, Jim Hartnett, Mei Cong, Jamison Grailer
Journal: Cancer Research (2025)

Abstract Personalized mRNA vaccines, designed with patient-specific tumor mutations, are now advancing in clinical trials and showing promising results. Additionally, the delivery of therapeutic proteins (e.g., antibodies) encoded by mRNA is under active development. The large-scale production of mRNA is through the process of in vitro transcription (IVT). A significant byproduct and contaminant of IVT is double-stranded RNA (dsRNA), which is highly immunogenic. dsRNA can trigger inflammation, induce cell death, and inhibit protein translation. Therefore, accurate quantification of dsRNA is essential to ensure the safety and efficacy of mRNA therapeutics. However, current technologies, such as dot blot and ELISA, lack the sensitivity and quantitation needed for robust dsRNA detection. In this work, we describe the development of novel luminescent assays for the sensitive and specific quantitation of dsRNA in IVT products. First, we applied NanoBiT® split luciferase technology to detect dsRNA in mRNA drug substance. In this assay, dsRNA-binding domains are fused to the SmBiT and LgBiT components of NanoBiT®. In the presence of dsRNA, these domains dimerize, reconstituting a functional NanoBiT® luciferase enzyme that generates light proportional to the dsRNA concentration. The assay detects dsRNA longer than 30 base pairs and is agnostic to sequence and size. It exhibits high specificity, with no cross-reactivity to single-stranded RNA or DNA, and a limit of quantitation below 10 pg/ml. As a complementary approach, we developed a cell-based bioassay to detect encapsulated dsRNA within LNPs. Upon endocytosis, LNP-encapsulated dsRNA is recognized by Toll-like receptor 3 (TLR3). This activation is captured via a TLR3-specific promoter driving luciferase expression, offering a physiologically relevant readout of dsRNA bioactivity. Both assays are streamlined in an “add-mix-read” format, requiring no wash steps or media transfers, and deliver robust, sensitive, and reproducible performance. Together, these tools enable precise detection of dsRNA contaminants in IVT products, ensuring the quality and safety of mRNA therapeutics. Citation Format: Rich Moravec, Jun Wang, Jim Hartnett, Mei Cong, Jamison Grailer. Development of novel luminescent assays for sensitive and specific quantitation of double-stranded RNA in mRNA vaccines [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 5479.
Abstract 6325: Zeaxanthin augments CD8+ effector T cell function by enhancing TCR stimulation
Authors: Freya Q. Zhang, Jiacheng Li, Rukang Zhang, Jiayi Tu, Zhicheng Xie, Takemasa Tsuji, Hardik Shah, Matthew O. Ross, Ruitu Lyu, Junko Matsuzaki, Kelly Xue, Fatima Choudhry, Chunzhao Yin, Hamed R. Youshanlouei, Syed Shah, Michael W. Drazer, Marc Bissonnette, Yuancheng Li, Hui Mao, Jun Huang, Lei Dong, Rui Su, Chuan He, Kunle Odunsi, Jing Chen, Hao Fan
Journal: Cancer Research (2025)

Abstract The evolution of diet has played an essential role in shaping human physiology and pathology, including the development of the immune system and responses to environmental stimuli. However, the specific mechanisms underlying the regulatory significance of dietary components in modulating anti-tumor immunity remain largely unknown. Here, we applied a co-culture screen approach using a blood nutrient compound library to identify zeaxanthin, a dietary carotenoid pigment found in many fruits and vegetables that is important for eye health, as an immunomodulator that enhances cytotoxicity of CD8+ T cells against tumor cells. Oral zeaxanthin, but not lutein, a zeaxanthin structural isomer, enhances anti-tumor immunity in vivo. Integrated multi-omics mechanistic studies reveal that zeaxanthin directly promotes T-cell receptor (TCR) stimulation on CD8+ T cell surface, leading to improved intracellular TCR signaling for effector T cell function. Hence, zeaxanthin treatment augments effectiveness of immune checkpoint inhibitor in vivo and human TCR-engineered CD8+ T cells to induce cell death against co-cultured tumor cells. Our findings uncover a previously unknown immunoregulatory function of zeaxanthin, which has translational potential as a dietary element in bolstering immunotherapy. Citation Format: Freya Q. Zhang, Jiacheng Li, Rukang Zhang, Jiayi Tu, Zhicheng Xie, Takemasa Tsuji, Hardik Shah, Matthew O. Ross, Ruitu Lyu, Junko Matsuzaki, Kelly Xue, Fatima Choudhry, Chunzhao Yin, Hamed R. Youshanlouei, Syed Shah, Michael W. Drazer, Marc Bissonnette, Yuancheng Li, Hui Mao, Jun Huang, Lei Dong, Rui Su, Chuan He, Kunle Odunsi, Jing Chen, Hao Fan. Zeaxanthin augments CD8+ effector T cell function by enhancing TCR stimulation [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 6325.
Abstract 6292: Highly sensitive detection of circulating-tumor DNA in plasma using whole genome sequencing
Authors: Sven Bilke, Alex Buerkle, Christine Eng, Theo Heyns, Yuka Suzuki, Yunjiao Zhu, Yuan Ding, Jacob Gibson, Artem Movsesyan, Heather Talia, Pete Taylor, Jacquelyn Truong, Jeff Tsai, Li Liu, Khai Luong
Journal: Cancer Research (2025)

Abstract Sensitive detection of circulating-tumor DNA (ctDNA) in plasma is increasingly utilized as a biomarker of minimal residual disease (MRD) in assessing oncology therapy response, relapse detection, and as a surrogate endpoint in clinical trials for solid tumors. Both tumor-naïve and informed MRD strategies have been described in literature, some of which are available commercially. Tumor-naïve MRD assays detect tumor-specific biomarkers in cfDNA without the patient’s tumor. Although tumor-naïve approach is beneficial in non-resectable tumor cases, tumor-informed assays are generally more sensitive. In a tumor-informed approach, the tumor-specific variants (SNV, indels, MNV, CNV, SV, methylation, etc.) are determined from a patient’s tumor and matched-normal, which are subsequently monitored in the patient’s cell-free DNA (cfDNA) using a patient-specific bespoke panel, a fixed panel, or whole genome sequencing (WGS). Amongst the tumor-informed approaches, tracking tumor mutations in cfDNA with patient-specific bespoke probes has become a popular approach due to its potential for high analytical accuracy and low sequencing cost. However, bespoke approaches require high DNA input for high accuracy, longer turnaround times, and operational complexity when running a patient-specific assay. Fixed, small panels have the potential to improve operational efficiency and reduce turnaround time. But creating a panel with high sensitivity across multiple tumor types can be a challenge due to tumor type specific mutational rates and patterns. We have developed a simple tumor-informed multi-cancer WGS method that can detect ctDNA down to 10 ppm with low DNA input requirements. WGS of a patient’s tumor and matched-normal yields a patient and tumor-specific set of somatic variants for MRD detection. These variants can then be monitored in the plasma using low-pass WGS. Because the WGS data inherently contains the genomic signatures of the tumor, additional biomarkers beyond SNVs that may be more salient of certain cancer types may be additionally assessed without the need to redesign the assay. We demonstrate that this technique can work across a range of tumor mutational burden (TMB) and various tumor types, achieving detection in the range of 10-100ppm. Citation Format: Sven Bilke, Alex Buerkle, Christine Eng, Theo Heyns, Yuka Suzuki, Yunjiao Zhu, Yuan Ding, Jacob Gibson, Artem Movsesyan, Heather Talia, Pete Taylor, Jacquelyn Truong, Jeff Tsai, Li Liu, Khai Luong. Highly sensitive detection of circulating-tumor DNA in plasma using whole genome sequencing [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 6292.
Abstract 6273: AI-based serum proteomics models predict survival outcomes in NSCLC patients undergoing immunotherapy
Authors: Junho Song, Leeseul Kim, Donghoon Shin, Jongwoo Kim, Taegyu Um, Allen Cho, Jaeyoung Bae, Liam IL-YOUNG Chung, Jeeyeon Lee, Young Kwang Chae
Journal: Cancer Research (2025)

Abstract Background: Clinical responses to immune checkpoint inhibitors (ICIs) are highly variable. Pre-treatment serum proteomic biomarkers offer a promising tool to predict response outcomes by capturing the biological mechanisms underlying response variability. Methods: This retrospective cohort study analyzed pre-treatment serum samples from 158 consecutive locally advanced or metastatic (palliative intent treatment) NSCLC patients treated with ICI monotherapy or ICI-chemotherapy combination. Deep proteomic profiling via mass spectrometry identified protein interaction patterns, and three machine learning models—XGBoost, logistic regression, and multilayer perceptron (MLP)—were evaluated using 5-fold cross-validation. The primary outcomes were progression-free survival (PFS) and overall survival (OS) at multiple time points (3, 6, 9, 12, 36, and 60 months), with performance assessed using the area under the receiver operating characteristic curve (AUC). Results: The study group had a median age of 70.8 years, with 51.9% female and 67.7% with adenocarcinoma. Smoking history showed 15.8% never smoked, 69.6% were former smokers, and 13.9% were current smokers. Performance status (PS) was 0 in 19.0%, 1 in 54.4%, 2 in 19.6%, and 3 in 5.7%. The median tumor mutational burden (TMB) was 5.3 mut/Mb, with PD-L1 &amp;lt;1% in 31.6%, &amp;gt;1% in 55.7%. Treatment regimens included mono-ICI (38.0%), dual ICI (13.9), and ICI + chemotherapy (48.1%). Median OS was 19.5 months, PFS was 6.6 months. Proteomic-based models showed varying performance across outcomes and time points. For PFS, XGBoost achieved the highest performance at 90 days (AUC=0.67), maintaining moderate prediction at 270 days (AUC=0.65) and 1 year (AUC=0.65). For OS, performance improved over time, with the best results at 1 year (AUC=0.61). Using 4, 000 highly variable proteomic mass spectrometry features, risk stratification at 1 year OS showed significant differences between groups (log-rank p=0.05) in PFS, with median PFS of 187 and 283 days for high- and low-risk groups, respectively (HR=1.38, 95% CI: 0.95-2.02, log-rank p=0.09). Conclusion: Serum proteomics-based AI model can predict PFS and OS in NSCLC patients treated with ICIs, achieving AUCs up to 0.67 for PFS and 0.61 for OS. Larger studies are needed to validate our findings. Citation Format: Junho Song, Leeseul Kim, Donghoon Shin, Jongwoo Kim, Taegyu Um, Allen Cho, Jaeyoung Bae, Liam IL-YOUNG Chung, Jeeyeon Lee, Young Kwang Chae. AI-based serum proteomics models predict survival outcomes in NSCLC patients undergoing immunotherapy [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 6273.
Abstract 6337: A novel PMS2 mutant Lynch syndrome mouse model for cancer prevention studies
Authors: Kajal Biswas, Yurong Song, Vaishnavi Peddibhotla, Brandon Somerville, Mary Albaugh, Dillon Dierman, Rameesha Mustafa, Altaf Mohammed, Shyam K. Sharan, Robert H. Shoemaker
Journal: Cancer Research (2025)

Abstract Mono-allelic germline pathogenic variants (GPVs) in MMR genes (MLH1, MSH2, PMS2, and MSH6) predispose individuals to hereditary non-polyposis colorectal cancer (HNPCC), better known now as Lynch syndrome (LS). Bi-allelic GPVs in MMR genes lead to a severe phenotype, constitutional MMR deficiency (CMMRD), that is characterized by early onset of leukemia/lymphoma, colorectal/gastrointestinal tumors, brain tumors, and sarcomas. MMR deficient mouse models have provided many mechanistic and translational insights. Pms2-null (Pms2ko/ko) mice were found to be viable but showed an increase in microsatellite instability and developed lymphomas and sarcomas. One of the most frequently occurring human mutations in PMS2 is a founder mutation NM_000535.5:c.2002A&amp;gt;G (p.I668V), observed in the Canadian Inuit population (1 in 16 Inuits are carriers). This mutation acts as a de novo splice site that creates a 5 bp deletion resulting in a truncated protein (p.I668*). A mouse model with an equivalent germline mutation (Pms2c.1993A&amp;gt;G) results in a splicing defect like that observed in humans and exhibits a significant increase in microsatellite instability and intestinal adenomas on an Apc mutant (Apctm1Rak ) background. We are now further characterizing this model for intestinal tumor initiation and progression using time course experiments and comparing tumor development by histopathological examination with the Pms2ko/ko model. Moreover, we are also examining this model to identify neoantigens, that may lead to development of a new vaccine for PMS2 mutation carriers.This mouse model can be a valuable tool to test the efficacy of new strategies for cancer prevention in PMS2 mutation carriers. We have developed a luciferase based splicing reporter assay in HEK293 cells that can be used to screen splicing modulators to suppress aberrant splicing of this splice site mutation. The efficacy of these modulators to suppress aberrant splicing in the small intestine of mice can be further tested using this mouse model. Citation Format: Kajal Biswas, Yurong Song, Vaishnavi Peddibhotla, Brandon Somerville, Mary Albaugh, Dillon Dierman, Rameesha Mustafa, Altaf Mohammed, Shyam K. Sharan, Robert H. Shoemaker. A novel PMS2 mutant Lynch syndrome mouse model for cancer prevention studies [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 6337.
Abstract 3360: Pre- and post-operative analysis of circulating tumor DNA in patients with breast cancer treated with neoadjuvant therapy using a tissue-free, methylation-based approach
Authors: Arielle J. Medford, Justine Knape, Derek Dustin, Haiyang Zhang, Caroline Weipert, Shivahamy Maheswaran, Irene Kuter, Jeffrey Peppercorn, Seth Wander, Steven J. Isakoff, Beverly Moy, Dejan Juric, Laura M. Spring, Aditya Bardia
Journal: Cancer Research (2025)

Abstract Background: Detection of circulating tumor DNA (ctDNA) in early breast cancer (BC) is a prognostic biomarker for disease recurrence. This pilot study evaluates the performance of a tissue-free epigenomic ctDNA assay in pre-neoadjuvant therapy (NAT), on-NAT and post-op plasma samples from patients (pts) with BC. Methods: Pre-NAT, on-NAT and post-op plasma samples from 13 pts that received NAT for BC were retrospectively analyzed for ctDNA using Guardant Reveal powered by Infinity, a tissue-free assay that analyzes differentially methylated regions of DNA using an applied bioinformatics filter optimized to detect BC. It results in binary ctDNA detection calls and a quantitative estimate of tumor fraction (TF) in ctDNA+ samples. Results: A total of 27 samples from 14 pts were evaluated, with 96% (26/27) samples passing quality control and included in the analysis (10 pre-NAT, 3 on-NAT, and 13 post-op). ctDNA was detected in 42% (11/26) of samples: 70% (7/10) pre-NAT, 33% (1/3) on-NAT and 23% (3/13) post-op (Table). For post-op samples collected within one year of recurrence, sensitivity was 100% (3/3). 2/5 pts who experienced recurrence, whose post-op samples were collected during adjuvant therapy and were ctDNA-, had a recurrence &amp;gt;15 months after the sample collection. No pts (0%, 0/8) without recurrence were ctDNA+ post-op. A pt with a brain-only recurrence had the lowest TF fraction amongst ctDNA+ post-op samples at 0.9%, with a median post-op TF of 2.5% (range, 0.9-23%) among the 3 ctDNA+ samples. Conclusion: ctDNA was detectable in 70% of pts pre-NAT, 33% on-NAT and 23% post-op, with persistent ctDNA associated with recurrence. In the subsequent full study, ∼ 600 samples will be evaluated at these timepoints. The dataset will provide a rich clinical landscape to understand sensitivity and specificity of methylation-based ctDNA testing, optimal timing and key areas to study therapeutic interception. Citation Format: Arielle J. Medford, Justine Knape, Derek Dustin, Haiyang Zhang, Caroline Weipert, Shivahamy Maheswaran, Irene Kuter, Jeffrey Peppercorn, Seth Wander, Steven J. Isakoff, Beverly Moy, Dejan Juric, Laura M. Spring, Aditya Bardia. Pre- and post-operative analysis of circulating tumor DNA in patients with breast cancer treated with neoadjuvant therapy using a tissue-free, methylation-based approach [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 3360.