bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C012: Integration of social variables resolves subclasses of tumor microenvironment
Authors: Hamilton Alina M. , McCormack Kara , Emerson Marc A. , Troester Melissa A. , Hyslop Terry 
Published: December 2023

Abstract
Intro: Recent work has identified subclasses of the tumor microenvironment, with most work emphasizing a robust adaptive immune response associated with ER-negative and/or basal-like tumors. Since adaptive immune responses may influence response to chemotherapy and may be targetable by immunotherapy, understanding population-level heterogeneity in immune response is important. Methods: We leveraged the Carolina Breast Cancer Study (CBCS), a large population-based study that oversampled young (≤50 years) and Black women with invasive breast cancer (BC). We performed NanoString gene expression profiling on tissue from 1,329 BC patients, including 704 (53%) Black and 625 (47%) non-Black women, and assayed genes representative of at least 10 individual immune cell types from both adaptive and innate arms of the immune system, homologous recombination deficiency signature and TP53 mutation status. Using a latent class approach that included variables for self-reported race, triple negative status, individual measures of socioeconomic status and community-level measures of advantage and disadvantage, we identified latent classes that integrated tumor microenvironment with tumor biology, individual and community level exposures under a Cells-to-Society conceptual model of breast cancer outcomes. Results: Latent Class Analysis identified 6 integrated classes of the tumor microenvironment, further subdividing a previously identified and validated adaptive immune class into two subgroups. The two adaptive classes were distinguished by different expression levels of B-cells, CD8+ T cells, cytotoxic cells and PD-L1, and differing frequency of basal-like subtype (Adaptive Class 1 RFD [95% CI]: 19.0 [11.9, 26.2]; Adaptive Class 2 RFD [95% CI]: 32.8 [23.3,42.3]) and presence of genomic instability gene expression subtypes (Adaptive Class-1 RFD [95% CI]: 22.1 [14.0, 30.1]; Adaptive Class-2 RFD [95% CI]: 37.5 [28.1,46.2]) relative to the immune-quiet tumors. Discussion: Social variables have complex effects on tumor biology and microenvironment, but latent class models and other model-based approaches may help to integrate biological data with other social factors to identify susceptible subgroups and to optimize precision medicine in diverse populations.
Citation Format: Alina M. Hamilton, Kara McCormack, Marc A. Emerson, Melissa A. Troester, Terry Hyslop. Integration of social variables resolves subclasses of tumor microenvironment [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C012.
Abstract C020: Racial differences in distress levels among Black and White hormone receptor–positive breast cancer survivors over a 3-year period
Authors: Tariq Fariha , Taylor Teletia , Perera Robert A. , Sheppard Vanessa B. 
Published: December 2023

Abstract
Purpose: The purpose of this study was to determine longitudinal racial variations in distress levels among Black and White women with hormone receptor-positive (HR+) breast cancer. Methods: This is a secondary data analysis from the Women’s Hormonal Initiation and Persistence (WHIP) Study, an observational study of HR+ breast cancer survivors. Data regarding patient demographics (e.g., race, age, education, income) were collected via surveys. Clinicopathologic factors (e.g., stage, type of surgery, chemotherapy, and radiation) and medication type (tamoxifen vs. aromatase inhibitors) were extracted from medical records. The National Comprehensive Cancer Network’s Distress Thermometer was used to capture distress following AET initiation at 4 timepoints (baseline, year 1, year 2 and year 3). Mixed linear effects models were used to identify differences in distress by race over the 3-year period. An unadjusted model included race and time as covariates, whereas the adjusted model controlled for demographics, clinicopathologic factors and medication type. Results: The total sample was comprised of 572 women (410 White and 162 Black). For the unadjusted model, the race by time interaction was not statistically significant (F3, 1002.53= 2.2895, p = 0.077). However, the race by time interaction was statistically significant in the adjusted model (F3, 670.99 = 2.68, p = 0.04576), such that Black survivors experienced increased distress over time compared to White survivors. Age was the only statistically significant covariate as older women had lower distress compared to their younger counterparts (p= 0.01) Conclusion. Black and White HR+ breast cancer survivors had different distress levels over a 3-year period. Over time Black survivors’ distress remained high compared to their White counterparts. It is important to consider these differences, given that Black women have higher breast cancer related morbidity and mortality. Future work should focus on the development of culturally appropriate interventions for distress management in HR+ Black breast cancer survivors.
Citation Format: Fariha Tariq, Teletia Taylor, Robert A. Perera, Vanessa B. Sheppard. Racial differences in distress levels among Black and White hormone receptor–positive breast cancer survivors over a 3-year period [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C020.
Abstract C031: ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers
Authors: Reams Romonia Renee , Heyliger Simone , Saulsbury Marilyn 
Published: December 2023

Abstract
The ABC transporters represent the largest family of transmembrane proteins. They also serve in protective roles whereby many transporters act as efflux pumps for xenobiotics. And subsequently, several members; most notably of the A, B and C subfamilies, have been implicated in cancer chemoresistance; however, D family members have not been extensively studies with regards to cancer biology and treatment. Here we report that ABCD3 transporter expression is upregulated in breast cancer (p&lt;0.001). The gene was also upregulated across cancer stages (p&lt;0.05). Analysis of histological subtypes revealed that ABCD3 was expressed infiltrating ductal carcinoma (IDC). Immunohistochemistry (IHC) analysis confirmed that ABCD3 protein is expressed IDC (p&lt;0.001). Moreover, ABCD3 expression was elevated in White (p&lt;0.001) and Asian (p&lt;0.05) breast cancer patients but not in African-American patients. Analysis of molecular subtypes revealed that ABCD3 expression was significantly higher in the Luminal breast cancer subtype (p&lt;0.001). Furthermore, ROC analysis of gene expression in relationship in response to treatment revealed that ABCD3 is a moderate predictor (AUC=0.644, p=0.003) of response to endocrine therapy (tamoxifen and aromatase inhibitors) and a strong predictor (AUC=08, p=0.026) to chemotherapy in luminal breast cancers. Taken collectively, ABCD3 represents a biomarker which may be important for determining therapeutic response.
Citation Format: Romonia Renee Reams, Simone Heyliger, Marilyn Saulsbury. ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C031.
Abstract C037: Bile acid modulation of immune cell interactions in the colonic microenvironment
Authors: Dai Hanchu , Wolf Patricia , Mutlu Ece , Tussing-Humphreys Lisa , Ridlon Jason , Gaskins Rex 
Published: December 2023

Abstract
Colorectal cancer (CRC) is the third most frequent cancer in both women and men, particularly among African Americans (AA). Factors such as ethnicity group, gut microbiota, and Western diet play a significant role in CRC development. However, the impact of ethnicity on the immunological mechanisms involved in CRC is poorly understood. In our study, we collected stool and serum samples from high-risk and low-risk AA and NHW subjects to analyze the fecal bile acid metabolome. We found that certain bile acid isoforms, particularly in allo-bile acids, were significantly reduced in the stool compared to Non-Hispanic White (NHW) females. Clinical mucosal RNA data we generated via the NanoString nCounter platform, revealed in both AA and NHW low-risk female groups, the expression of FoxP3, correlated with immune checkpoints including PDCD1, IDO1, CTLA4 and LAG3 were lowered. Recent findings suggest that allo-bile acids influence the balance between pro-inflammatory TH17 cells and anti-inflammatory Tregs through specific signaling pathways. Based on our data and existing literature, we propose that bacterial-derived allo-bile acids modulate interactions between other myeloid-lineage immune cells, thereby affecting the inflammatory environment of the colon and potentially influencing CRC development.
Citation Format: Hanchu Dai, Patricia Wolf, Ece Mutlu, Lisa Tussing-Humphreys, Jason Ridlon, Rex Gaskins. Bile acid modulation of immune cell interactions in the colonic microenvironment [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C037.
Abstract C040: Single cell analysis of circulating peripheral blood mononuclear cells in African American men with prostate cancer and their association with lethal disease
Authors: Ahmed Md Shakir U. , Dorsey Tiffany , Ambs Stefan 
Published: December 2023

Abstract
Prostate cancer is a leading cause of cancer-related deaths among men in the United States and affects African American (AA) men more so than other men. We and others previously described a distinct tumor immunobiology in AA prostate cancer patients. Furthermore, we discovered a serum proteome-defined suppression of tumor immunity signature that is prevalent among these patients and associated with lethal prostate cancer. In the current study, we sought to investigate the composition of circulating peripheral blood mononuclear cells (PBMCs) in AA and European American (EA) prostate cancer patients and their association with patient group and lethal prostate cancer. We obtained high-quality RNA-sequencing data for 277642 single cells representing circulating PBMCs from 59 AA and EA men. In the analysis, being an AA patients associated with an increased abundance of exhausted CD8+T cells and higher numbers of macrophages that classified as tumor-associated macrophages, whereas metallothionine-expressing macrophages were decreased in these men. Gene signatures indicative of T cell exhaustion were generally elevated in AA PBMCs while T cell effector function features were decreased. Within the myeloid cell population, cytokine and NFKB signatures were more prevalent in AA than EA patients. This gene signature pattern that we observed in AA patients also associated with lethal prostate cancer, namely the T cell exhaustion and elevated cytokine gene signatures, pointing to potential clinical implications. Lastly, the interferon-induced transmembrane protein (IFITM3), interferon alpha inducible protein (IFI6), cysteine rich protein-1 (CRIP1), and the RAC family small GTPase2 (RAC2) were notably upregulated in AA patient-derived immune cells. In summary, we show that circulating immune cell populations and the associated gene signatures differ between men of African and European descent. Those elevated in AA patients correlated with lethal prostate cancer.
Citation Format: Md Shakir U. Ahmed, Tiffany Dorsey, Stefan Ambs. Single cell analysis of circulating peripheral blood mononuclear cells in African American men with prostate cancer and their association with lethal disease [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C040.
Abstract C041: Transcriptomic analysis of prostate cancer patients living with HIV
Authors: Song Hanbing , Li Michelle , Akutagawa Jon , Huang Franklin 
Published: December 2023

Abstract
Background: Higher incidence and mortality rates of liver, lung, anal, and head and neck cancers are typically seen in patients living with human immunodeficiency virus (HIV). However, some previous studies have a decreased risk of prostate cancer in HIV+ patients, particularly in men from sexual minorities, with no clear biological or epidemiological explanation. Methods: To identify the specific transcriptomic changes and genetic pathways associated with HIV infection and prostate cancer emergence, we performed bulk RNA-Seq analysis on 18 prostate cancer samples (9 HIV+ and 9 HIV-). We first used kallisto to measure gene-level expression. We then performed principal component analysis (PCA) to determine if HIV status clearly clustered patients based on their gene expression levels. We subsequently used DESeq2 to perform differentially expressed transcriptomic analysis to identify genes that are associated with HIV and prostate cancer phenotypes. Samples were clustered based on expression levels of the top differentially expressed genes across the HIV+ and HIV- phenotypes. Gene set enrichment analysis was performed on the gene signatures from the two phenotypes. Using an existing single cell RNA-Seq prostate cancer dataset, we deconvoluted the 18 samples with CIBERSORT to approximate the cell type composition. Results: PCA highlighted no major separation between samples based on HIV status. We identified 450 significantly upregulated genes in HIV+ patients, including YAP1, MAT2A, KLF4, and ERF. We identified 409 upregulated genes in HIV- patients, including MICA, AQP2, and KRT6C. Upregulated genes found in HIV+ patients were significantly enriched in multiple immune response pathways, which is consistent with previous sequencing studies focused on HIV status. After cell type composition estimation, we found the samples to be similar in their cell type distributions - stromal and tumor cells were the largest populations, while immune cells were not well represented. Conclusions: We identified transcriptomic differences that need future studies that directly interrogate the biological pathways that affect the incidence of prostate cancer in patients living with HIV.
Citation Format: Hanbing Song, Michelle Li, Jon Akutagawa, Franklin Huang. Transcriptomic analysis of prostate cancer patients living with HIV [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C041.
Abstract C048: Single-cell RNA sequencing analysis in prostate cancer patients from African ancestry
Authors: Song Hanbing , Chen Yih-An , Yue William , Weinstein Hannah N.W. , Allegakoen Paul , Yang Heiko , Kim Emory , Pham Julia , Hui Keliana , Cooperberg Matthew R. , Huang Franklin W. 
Published: December 2023

Abstract
Prostate cancer is the second most common malignancy in men worldwide. Men of African ancestry (AA) have a higher incidence rate and increased prostate cancer mortality, present with more advanced disease at earlier ages, than men of European ancestry (EA). Aside from socioeconomic factors driving this disparity, genomic factors also greatly contribute to the differences in the incidence and mortality rates. Despite recent advancements in comparisons of genomic alterations, a comprehensive transcriptomic and epigenomic landscape of tumors from AA prostate cancer patients has yet to be developed. Droplet-based single-cell technologies have evolved and now enabled the profiling of transcriptome, epigenome, and chromatin organization from complex tissues at single-cell resolution. To identify cell populations with distinctive molecular features and cell-type specific transcriptional programs and cell states from AA prostate cancer patients, we performed single-cell RNA sequencing for 11 EA and 6 AA prostate cancer patients. By investigating the differentially expressed genes in a cell-type-specific manner between AA and EA patients, we found that endothelial and myeloid cell populations showed significant enrichment of inflammatory pathways in AA patients. In the analysis, we also identified a group of heat shock protein family genes that were upregulated in AA patients in multiple cell types. Then, ligand-receptor interactions between tumor cells and immune microenvironments from AA and EA prostate cancer patients identified significant interactions involving frizzled receptors (FZD) that were enriched in AA patients. Overall, the transcriptomic differences may reveal oncogenic mechanisms in AA prostate cancer patients compared to EA patients.
Citation Format: Hanbing Song, Yih-An Chen, William Yue, Hannah N.W. Weinstein, Paul Allegakoen, Heiko Yang, Emory Kim, Julia Pham, Keliana Hui, Matthew R. Cooperberg, Franklin W. Huang. Single-cell RNA sequencing analysis in prostate cancer patients from African ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C048.
Abstract C050: Allele-specific expression analysis identifies novel dysregulated genes in high-risk prostate tumors from African-American men
Authors: Tsui Margaret , Hu Kevin , Song Hanbing , Huang Franklin W. 
Published: December 2023

Abstract
African-American (AA) patients are twice as likely to die from prostate cancer (PCa) compared to European American (EA) patients. Racism, socioeconomic status, access to healthcare, and tumor biology have been attributed to this mortality gap. Tumor biology has not been fully characterized in AA patients, particularly the landscape of gene-regulatory alterations and how they may contribute to tumor aggressiveness. We use allele specific expression (ASE) analysis, which detects genes showing imbalanced expression of alleles often due to altered gene regulation on one allele, to comprehensively identify dysregulated genes in high-risk PCa tumors from AA patients. We develop a framework for identifying candidate cancer genes by integrating ASE data, clinical data, and epigenetics. Our approach identifies genes that recurrently undergo ASE across AA patient tumors. Further, we describe genes that more frequently undergo ASE in AA patient tumors compared to EA patient tumors, some of which are implicated in hormone therapy resistance, aggressive disease, and worse disease-free survival. Our work demonstrates the potential for ASE to uncover dysregulated genes that may not have been identified through RNAseq alone. Ultimately, this work increases our understanding of the effects of regulatory alterations in tumors and how they may contribute to disparities in PCa.
Citation Format: Margaret Tsui, Kevin Hu, Hanbing Song, Franklin W. Huang. Allele-specific expression analysis identifies novel dysregulated genes in high-risk prostate tumors from African-American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C050.
Abstract C059: Optimization of DNA extraction methods from FFPE prostate tumor tissues of Black men to identify DNA methylation biomarkers
Authors: Stensrud Colton , Stevens Claire , Gonzalez-Smith Leonardo , Cao Huan , Buxbaum Sarah , Falzarano Sara , Rhie Suhn 
Published: December 2023

Abstract
Prostate cancer is the second leading cause of cancer related deaths among men in the United States, and health disparities in those diagnosed with prostate cancer are observed between those of African and European ancestry. Our approach to understand the mechanisms underlying these differences is to compare DNA methylation profiles between samples using formalin-fixed parafin-embedded (FFPE) prostate tumor tissues. To profile DNA methylation from FFPE prostate tumor tissues, we tested magnetic bead and column based DNA extraction methods, and evaluated them on their total DNA yield. Additionally, we assessed the relationship between DNA yield and clinical features. Prostate specimens for this study were obtained from the University of Florida in the form of FFPE tissue slides. Both tumor and normal tissue regions were outlined on an H&E reference slide and the respective regions were macro-dissected from unstained slides of the same block. The areas of macro-dissected regions were measured using ImageJ, and the number of slides were taken to further normalize DNA yield. Magnetic bead and column based FFPE DNA extraction kits were used to isolate DNA, and the relative amounts of the isolated DNA per tissue size were evaluated. In addition, various clinical features of the samples were compared to determine if their presence influences DNA yield. Preliminary data suggests that total DNA extracted from both bead and column based methods are relatively comparable, but bead based methods yielded better quality of DNA. We observed minimal correlation between DNA yield and grade group. We detected a potential association between cribriform pattern and DNA yield. We are in the process of profiling DNA methylation using the isolated DNA. Successful completion of this study will identify DNA methylation biomarkers and further develop diagnostic and therapeutic tools for prostate cancer patients from African ancestry.
Citation Format: Colton Stensrud, Claire Stevens, Leonardo Gonzalez-Smith, Huan Cao, Sarah Buxbaum, Sara Falzarano, Suhn Rhie. Optimization of DNA extraction methods from FFPE prostate tumor tissues of Black men to identify DNA methylation biomarkers [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C059.