Dataset Information

Differences in gene-expression profiles in breast cancer between African and European-ancestry women.

ABSTRACT: African American (AA) women have an excess breast cancer mortality than European American (EA) women. To investigate the contribution of tumor biology to this survival health disparity, we compared gene expression profiles in breast tumors using RNA sequencing data derived from 260 AA and 155 EA women who were prospectively enrolled in the Southern Community Cohort Study (SCCS) and developed breast cancer during follow-up. We identified 59 genes (54 protein-coding genes and 5 long intergenic non-coding RNAs) that were expressed differently between EA and AA at a stringent false discovery rate (FDR) < 0.01. A gene signature was derived with these 59 genes and externally validated using the publicly available Cancer Genome Atlas (TCGA) data from180 AA and 838 EA breast cancer patients. Applying C-statistics, we found that this 59-gene signature has a high discriminative ability in distinguishing AA and EA breast cancer patients in the TCGA dataset (C-index = 0.81). These findings may provide new insight into tumor biological differences and the causes of the survival disparity between AA and EA breast cancer patients.

SUBMITTER: Ping J

PROVIDER: S-EPMC7359770 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Differences in gene-expression profiles in breast cancer between African and European-ancestry women.

Ping Jie J Guo Xingyi X Ye Fei F Long Jirong J Lipworth Loren L Cai Qiuyin Q Blot William W Shu Xiao-Ou XO Zheng Wei W

Carcinogenesis 20200701 7

African American (AA) women have an excess breast cancer mortality than European American (EA) women. To investigate the contribution of tumor biology to this survival health disparity, we compared gene expression profiles in breast tumors using RNA sequencing data derived from 260 AA and 155 EA women who were prospectively enrolled in the Southern Community Cohort Study (SCCS) and developed breast cancer during follow-up. We identified 59 genes (54 protein-coding genes and 5 long intergenic non ...[more]

PMID: 32267939

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Project description:ObjectivesDespite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored.Materials and methodsWe identified differentially spliced genes (DSGs) and differentially expressed genes (DEGs) in biobanked lung squamous cell carcinoma (LUSC) between patients of West African and European ancestry, using ancestral genotyping and Affymetrix Clariom D array. DSGs and DEGs were validated independently using the National Cancer Institute Genomic Data Commons. Associated biological processes, overlapping canonical pathways, enriched gene sets, and cancer relevance were identified using Gene Ontology Consortium, Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, and CancerMine, respectively. Association with LUSC survival was conducted using The Cancer Genome Atlas.Results4,829 DSGs and 267 DEGs were identified, including novel targets in NSCLC as well as genes identified previously to have relevance to NSCLC. RNA splicing events within 3 DSGs as well as 1 DEG were validated in the independent cohort. 853 DSGs and 29 DEGs have been implicated as potential drivers, oncogenes and/or tumor suppressor genes. Biological processes enriched among DSGs and DEGs included metabolic process, biological regulation, and multicellular organismal process and, among DSGs, ion transport. Overlapping canonical pathways among DSGs included neuronal signaling pathways and, among DEGs, cell metabolism involving biosynthesis. Gene sets enriched among DSGs included KRAS Signaling, UV Response, E2 F Targets, Glycolysis, and Coagulation. 355 RNA splicing events within DSGs and 18 DEGs show potential association with LUSC patient survival.ConclusionThese DSGs and DEGs, which show potential biological and clinical relevance, could have the ability to drive novel biomarker and therapeutic development to mitigate LUSC disparities.

Dataset Information

Differences in gene-expression profiles in breast cancer between African and European-ancestry women.

Publications

Differences in gene-expression profiles in breast cancer between African and European-ancestry women.

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