tbuckley/cabot-search huggingface dataset:
Abstract 842: Maize consumption and circulating aflatoxin B1 levels in Mexican adults
Authors: Martin Lajous, Obed Solis-Martinez, Adriana Monge, John Groopman, Katherine A. McGlynn, Martin Romero, Carolina Batis, Hector Lamadrid-Figeuroa, Horacio Riojas-Rodriguez
Journal: Cancer Research (2024)

Abstract Objective: To estimate the impact of maize consumption on aflatoxin B1 [AFB1] levels, a potent carcinogen, in Mexican adults living in south and eastern Mexico. Methods: Study participants were women and men ≥40 years of age living in five high hepatocellular carcinoma burden states who participated in Mexico’s 2018 National Health and Nutrition Survey, a stratified, multi-stage, and cluster survey probability sampling household survey that is representative of the Mexican population. We estimated the consumption of maize intake in grams per day using a previously validated semi-quantitative food frequency questionnaire with a time reference of the previous seven days. We determined circulating AFB1-albumin lysine adduct [AFB1-lys] levels in serum using liquid chromatography. Guided by subject-matter knowledge we fit multivariable linear regression models that considered the survey design and included age, sex, residence, ethnicity, education, socioeconomic status, and foods known to be contaminated with aflatoxins including peanuts, rice, dried chili, milk, and cheese. Results: Among the 915 participants, median maize consumption was 307 grams per day [Q1-Q3: 165 - 554]. Maize tortillas contributed 80% of the total maize consumption. The median maize tortillas consumption was 252 grams per day [Q1-Q3: 120 - 462], approximately 8 tortillas per day. Prevalence of AFB1-lys detection was 92% and median levels were 0.127 pg/µL [Q1-Q3: 0.052 - 0.449]. After adjusting for factors that may affect aflatoxin levels, for every 100 grams of maize consumption AFB1-lys levels were 7.4% [β: 0.071, 95% CI: 0.030 - 0.112] higher. And for every tortilla consumed [30 g of maize], we observed a 2.0% [β: 0.020, 95% CI: 0.006 - 0.034] higher level of circulating AFB1-lys. Conclusion: These findings indicate that maize and maize tortillas may be an important source of AFB1 exposure in the Mexican population. Mexico requires effective public health interventions to mitigate exposure to AFB1. Citation Format: Martin Lajous, Obed Solis-Martinez, Adriana Monge, John Groopman, Katherine A. McGlynn, Martin Romero, Carolina Batis, Hector Lamadrid-Figeuroa, Horacio Riojas-Rodriguez. Maize consumption and circulating aflatoxin B1 levels in Mexican adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 842.
Abstract 832: Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland
Authors: Peng Yunzhi Li
Journal: Cancer Research (2024)

Abstract Background: Radon as a common source of environmental radiation, while its carcinogenic effect on urinary tract cancer has not been fully investigated. Methods: Men and women who have continuously lived in Finland from year 1987 onward and reached 40+ years old at the beginning of 2017 were followed up for urinary tract cancer, including bladder cancer (ICD-O 3 code C67) and kidney cancer (C64-C66 and C68) for 5 years until the end of 2021. The residential location and type of buildings of the cohort members were traced from year 1987 until 2016 annually and linked to the average cumulative exposure of radon concentration in well water on municipality level. Newly diagnosed UTC cases were identified based on the Finnish cancer register. Pre-existing health conditions, such as hypertension, diabetes, chronic kidney disease, calculus of kidney and lower urinary tract, family history of cancer, as well as socioeconomic factors were ascertained from multiple registry databases. Data were analyzed with Cox proportional hazards model conditional on birth cohorts and adjusted with available covariates. Findings: Among 1,019,331 men and 1,192,960 women with 30-years average radon exposure, 4206 and 2226 urinary tract cancer cases were diagnosed during follow-up period from 2017 until correspondingly. Men with higher radon exposure (&amp;gt;500 Bq/m3) had about 14% higher risks of UTC in total (HR 1.14, 95% CI 1.07-1.21), 19% higher risks of bladder cancer (HR 1.19, 95%CI 1.09-1.32), 10% higher risks of kidney cancer (HR 1.10, 95%CI 1.02-1.20) comparing with lower exposed samples. Women with higher radon exposure had about 1% higher risks of UTC in total (HR 1.01, 95%CI 0.93-1.10), 3% higher risks of bladder cancer (HR 1.03, 95%CI 0.88-1.22), 1% higher risks of kidney cancer (HR 1.01, 95%CI 0.92-1.11). In the sub-population who only lived in houses during the 30-years exposure period, men with higher radon exposure had about 24% higher risks of UTC (HR 1.24, 95% CI 1.12- 1.36), 30% higher risks of bladder cancer (HR 1.30, 95%CI 1.12-1.51), 20% higher risks of kidney cancer (HR 1.20, 95%CI 1.06-1.36). No significant association was observed in women who only lived in houses during exposure period. Conclusions: For men, higher radon exposure was significantly associated with elevated risks of UTC. No significant association was observed in women. Further investigates were needed to explore the mechanisms of gender differences in UTC susceptibility associated with radon exposure. Keywords: Radon, Radiation, Cancer, Urinary tract cancer, Kidney cancer, Bladder cancer Citation Format: Peng Yunzhi Li. Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 832.
Abstract 1171: Estimating sensitivity of exploratory cellular biomarkers in oncology clinical trials
Authors: Chengsen Xue, Christina D. Swenson, Thomas W. Mc Closkey
Journal: Cancer Research (2024)

Abstract Background: In the prolonged and complex process of assessing immunotherapeutic oncology drug candidates, flow cytometry plays an essential role. In oncology studies, biomarker measurement requires robust and reliable flow cytometric assays. A crucial element of these assays is to understand the lower limits of measurable surface biomarkers. Methods: We incorporated into the development and validation of flow cytometry assays the measurement of the lower limit of quantitation (LLOQ). The LLOQ is the lowest number of a reportable parameter in a blood or bone marrow study sample that can be quantitatively determined with acceptable precision and accuracy. Two steps are necessary to determine the LLOQ. First in these assessments a measurable range of lower limits of a particular cell type or receptor is estimated. That is, in validating an assay LLOQ, there are three options to select cells expressing target surface biomarkers of interest: using cultured or bioengineered cells, using samples of known high expression of a biomarker, or using pre-titered positive samples. Then decreasing concentrations of the target cell or receptor may be used to precisely determine the LLOQ of a specific assay reportable parameter. Results: By acquiring at least ten negative control sample results, the limit of the blank (LOB) and limit of detection (LOD) of a biomarker is determined. LOB is calculated as mean +1.645 SD, and LOD as mean +3 SD. The negative control samples either lack the fluorescent monoclonal antibodies against the markers of interest or lack the target cell population. Different reportable parameters, detected by one or more biomarkers have varying LLOQ. The LLOQ for a reportable parameter is a precise measurement of a parameter above or equal to the LOD. We found that typical LLOQ values are from 4 to 145 positive cells, with a frequency of 0.01 to 0.1% among a parent population. For example, in the case of tetramer assays, flow cytometry can reliably detect as few as 25 CD8+ antigen-specific cells among three million lymphocytes. Conclusions: LLOQ determinations for exploratory flow cytometry biomarkers are required for clinical research in cancer immunotherapy and cancer vaccine development. This valuable information allows for interpretation of data at the low end of a measurable range. Citation Format: Chengsen Xue, Christina D. Swenson, Thomas W. Mc Closkey. Estimating sensitivity of exploratory cellular biomarkers in oncology clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1171.
Abstract 3007: AZGP1 inhibits angiogenesis in prostate cancer
Authors: Ru Wen, G Edward Wen, Zhengyuan Qiu, Eric E Peterson, Fernando Jose Garcia Marques, Abel Bermudez, Jonathan R Pollack, Hongjuan Zhao, Sharon Pitteri, James Brooks
Journal: Cancer Research (2024)

Abstract AZGP1 is involved in various biological processes, including lipid metabolism, regulation of cell proliferation, migration and invasion, and immune response. The loss of AZGP1 is associated with worse clinical outcomes, and AZGP1 has been indicated as a potential biomarker for prostate cancer. However, the underlying mechanisms of AZGP1 function in prostate cancer are unknown. This study reports AZGP1's pivotal involvement in angiogenesis within the prostate cancer tumor environment. Neither knockout nor overexpression of AZGP1 affects in vitro prostate cancer cell proliferation, migration, or invasion. Morphologically, AZGP1-deficient mouse prostates appear normal, but exhibit increased fibroblast growth in periglandular stroma after 6 months. The overexpression of AZGP1 does not impact the growth of PC3 and DU145 tumors; instead, these tumors significantly reduced microvessel density, suggesting AZGP1 exhibits anti-angiogenic properties. Proteomic profiling shows distinct profile of angiogenesis-related proteins between PC3-AZGP1-OV and PC3 control cells, featuring proteins like PDCD6 and MMP9. This study provides insights into the anti-angiogenic attributes of AZGP1 in prostate cancer, underscoring its potential as a therapeutic target for prostate cancer. Citation Format: Ru Wen, G Edward Wen, Zhengyuan Qiu, Eric E Peterson, Fernando Jose Garcia Marques, Abel Bermudez, Jonathan R Pollack, Hongjuan Zhao, Sharon Pitteri, James Brooks. AZGP1 inhibits angiogenesis in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3007.
Abstract 6226: Identifying nested spatial units as a conserved organizing principle of the spatial tumor microenvironment
Authors: Vivek Behera, Hannah Giba, Benjamin A. Doran, Justin P. Kline, Arjun S. Raman
Journal: Cancer Research (2024)

Abstract Heterogeneity of therapeutic response amongst cancer patients has a profound impact on cancer-related mortality. It has been widely hypothesized that diversity in clinical outcomes is driven by variability in tumor biology at scales ranging from inter-patient to inter-cellular. Indeed, the advent of technologies describing the tumor microenvironment (TME) at cellular resolution has demonstrated that TME organization is heterogeneous with respect to intra-tumor spatial location, body tumor location (primary vs metastatic), patient, and tumor type. However, the organizing principles that govern TME heterogeneity remain unclear. Without such organizing principles, it remains an arduous task to link descriptions of tumor biology heterogeneity to clinical outcomes in a mechanistically explainable manner. Through the application of network statistical inference models to spatial transcriptomic data, we have identified that nested spatial units (NSUs) are a core organizing principle of the TME. We find that NSUs are widely conserved across 96 patient biopsies of 14 distinct tumor types and 3 body locations (primary, abdominal metastases, brain metastases). Moreover, NSUs represent a transferrable organizing blueprint that allows for the spatial location of individual spots (5-50 cells) in a tumor biopsy to be predicted by the NSUs of a secondary, unrelated biopsy (Pearson correlation of spot-spot distance: 0.04 - 0.71, median 0.25). By using NSUs as the organizing unit of comparison, we identify variation in gene expression, biological pathways, and multicellular structures occurring across tumors in a distance-dependent manner. In summary, NSUs provide a foundation for the comparative analysis of tumor spatial biology and a path by which spatial biology can be mechanistically linked to patient outcomes. Citation Format: Vivek Behera, Hannah Giba, Benjamin A. Doran, Justin P. Kline, Arjun S. Raman. Identifying nested spatial units as a conserved organizing principle of the spatial tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6226.
Abstract 6207: Exploring colorectal cancer with ARIA: Biomedical insights
Authors: Nevena Nikolic, Sarah Kleinstein, Jelena Radenkovic, Milan Kovacevic
Journal: Cancer Research (2024)

Abstract Gaining the promised benefits from the population-scale datasets, both clinical and genomic, is often hindered by the inability to easily access, explore and manipulate such complex data - a difficulty that ARIA was designed to overcome. In the field of biomedicine, organizations harness extensive datasets, gaining profound insights into patients and participants, thereby unleashing possibilities for accelerating research, especially in the realms of drug development and precision medicine. To facilitate navigation through the intricate landscape of biomedical data, Velsera has innovated ARIA to catalyse efficient and insightful analysis, with a keen emphasis on user-friendliness to ensure accessibility across a diverse professional audience. To demonstrate the practical application of ARIA, we explore genomic and clinical datasets to identify key differences in colorectal cancer progression. CRC, the third most common cancer globally, has unique characteristics in origination and progression from benign to pathogenic. Here we investigate differences between patients with polyps that do and do not progress to CRC, including key environmental factors such as smoking history, inactive lifestyle and obesity in conjunction with their known clinical and genetic risk factors. This exploration into the abilities of ARIA demonstrate the ability to analyse complex datasets combining both clinical and genomics data at a large scale. For the purpose of this demonstration, a Synthea Dataset, encompassing synthetic clinical and genomic data for 122,011 patients across various age groups, was utilized. This dataset was generated by Velsera specifically for testing ARIA functionalities. In conclusion, ARIA empowers efficient analysis of complex biomedical datasets, providing a comprehensive understanding of disease mechanisms and facilitating valuable insights. Citation Format: Nevena Nikolic, Sarah Kleinstein, Jelena Radenkovic, Milan Kovacevic. Exploring colorectal cancer with ARIA: Biomedical insights [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6207.
Abstract 6218: Haplotype-resolved analysis of cancer genomes and epigenomes using Oxford Nanopore sequencing
Authors: Philipp Rescheneder, Phill James, Sean McKenzie, Andrea Talenti, Sergey Aganezov, Dan Turner, Sissel Juul
Journal: Cancer Research (2024)

Abstract Cancer is a complex and dynamic disease driven by somatic genomic and epigenomic alterations that accumulate over time. These changes give rise to heterogeneous collections of cells or clones, each with distinct (epi)genomic profiles within a single tumour. Accurate characterisation of these changes is crucial for understanding the mechanisms driving the disease, identifying potential therapeutic targets, and personalising treatment strategies. Due to the technological constraints of short-read and array-based approaches, cancer research has historically had a strong focus on detecting small genomic changes like SNPs and small indels (SNVs) as well as the broad characterisation of large-scale copy number changes (CNVs), mostly ignoring other important variant classes and epigenetic modifications. Here we demonstrate how Oxford Nanopore native long-read sequencing enables the direct detection of not only SNVs, but also break point-resolved simple and complex structural variants (SVs and CNVs), haplotype phasing of all variant types, and identification of DNA modifications like 5-methylcytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) from a single tumour-normal dataset. We illustrate how our end-to-end somatic workflow streamlines analysis for the different variant classes and benchmark somatic SNV and SV calling performance using well characterised cancer cell lines and in-silico benchmarking datasets at different sequencing depths. Finally, we use real-world tumour-normal pairs to showcase a comprehensive sample to answer tumour-normal analysis using Nanopore sequencing. This includes the characterisation of complex patterns of somatic SVs in the different cancer samples, the identification of unique 5mC methylation patterns, exploring characteristic differences in 5hmC levels between tumour and normal samples as well as showing how Nanopore long reads enable haplotype and clone specific CNV calling as well as phasing of genetic and epigenetic variation. Citation Format: Philipp Rescheneder, Phill James, Sean McKenzie, Andrea Talenti, Sergey Aganezov, Dan Turner, Sissel Juul. Haplotype-resolved analysis of cancer genomes and epigenomes using Oxford Nanopore sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6218.
Abstract 7364: Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion
Authors: Incheon Kang, Woo Young Kwon, Sung Hwan Lee
Journal: Cancer Research (2024)

Abstract Introduction: Microvascular invasion (MVI) is a well-known prognostic factor in predicting cancer relapse after curative resection of resectable hepatocellular carcinoma (HCC).Therefore, there is a clear unmet need for a precision strategy based on cancer-specific multi-omics features to predict the MVI feature at the initial diagnosis of HCC. Methods: Using gene expression profiling for resected human HCC (Discovery cohort, n=240), we identified the transcriptomic signature predicting the MVI feature. Comprehensive analyses were performed using the dataset from the cancer dependency map (DepMap) project, including cancer-specific molecular characterization with multi-omics data, and drug sensitivity with compound screening, and integrative in-silico prediction methods to uncover MVI. The transcriptomic signature predicting the MVI feature were validated in independent translational cohorts (TCGA-LIHC; n=373, KOREA; n=188, TOKYO; n=183, MODENA; n=78, ZHONGSHAN; n=159). Results: The MVI signature with 1028 genes was identified from robust statistical testing from the discovery cohort, and robust validation for the prediction performance of the MVI signature showed significant accuracy in the validation cohort (AUC=0.865, p&amp;lt;0.01). Multi-omics analysis revealed aggressive tumor biology associated with the MVI signature and specified biomarkers. Conclusions: Integrative multi-omics profiling for resectable HCC uncovers biomarkers to predict MVI. A novel combination of biomarkers performs in sorting out the tumor with aggressive tumor biology. A precision strategy to discover resectable tumors beneficial from surgical resection can be established from consecutive clinical trials based on this translational study. Citation Format: Incheon Kang, Woo Young Kwon, Sung Hwan Lee. Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7364.
Abstract 7358: Role of noncoding genome architecture in esophageal cancer
Authors: Hayriye Verda Erkizan, Robert Wadleigh
Journal: Cancer Research (2024)

Abstract Esophageal Cancer is a deadly disease with a tendency to be diagnosed at the later stages. Considered a rare disease, accounting for 1.1% of all cancers, EC comprises 2.6% of all cancer deaths. The survival rate for all stages is 21.7%. However, the survival rate decreases to 5.6 % for advanced-stage cancers. EC is more common in men and associated with older age and heavy alcohol and tobacco use. In the last 25 years, the death rate of EC has been decreasing slightly from 4.3 to 3.7. The death rates for lung, prostate, and colon cancers have decreased by half in the same time frame. Therefore, novel therapies and biomarkers are urgently needed to accelerate survival and reduce the death rates by at least half for patients with EC.We previously completed exome sequencing in a small sample size and observed that the mutations in the noncoding regions of the EC genome are highly affected. In this study, we perform exome sequencing in 110 paired esophageal tumors and normal tissues using an Agilent SSELXT HS Exon V8+UTR library enrichment kit. Twelve paired EC and normal tissues are sequenced using the PacBio Hifi system.In WES, we detected almost half of the noncoding region mutations in the 3UTR and 2kb downstream regions of the genome, significantly affecting 51 oncogenic or tumor suppressor genes. In addition, the involved genes are over-represented in critical signaling pathways and transcriptional regulation of pluripotent stem cells. The number of changes in the 5UTR and 2kb upstream are similar to the number of variations in the intronic regions. Apoptosis, stress response, and DNA double-strand break repair pathways are affected by 5UTR mutations. Mutations in the intronic regions frequently occurred in pro-tumorigenic immune regulation genes, such as IL-33 and IL-6, and oncogene-induced senescence.The combined effect of these genetic and coding region mutations on oncogenes, significant signaling pathways, cancer cell stemness, DNA damage repair pathways, and immune system regulation may significantly impact poor prognosis in EC patients. Further studies will verify the effectiveness of targeting these genes for developing candidate therapeutics. Citation Format: Hayriye Verda Erkizan, Robert Wadleigh. Role of noncoding genome architecture in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7358.