Transcriptomic Analysis of Primary Breast Cancer Utilizing Gene Expression Datasets from Middle-aged Caucasian Women
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Breast cancer due to its genetic and clinical diversity across various subtypes often presents overlapping molecular profiles. Despite evolving classification methods, it still poses challenges for accurate prognosis. The present study addresses this challenge by identifying genes associated with each clinical subtype through a comprehensive differential expression analysis. As a representative example of breast cancer, the expression dataset (SRA Project: SRP375823) was sourced from middle-aged Caucasian/European women. First, samples were categorized according to histological types, stratified into Luminal-A, -B, and HER2 enriched tumours, as well as based on EMT properties (presence or absence of circulating tumour cells (CTCs)) and p53 mutation status (presence or absence of P53 mutation). The entire differential expression analysis was conducted utilizing GATK and Tuxedo II pipelines, followed by functional enrichment analysis. Upon comparison with healthy controls, genes like mTOR, BARD, MYH10, APC exhibited significant associations with breast cancer. Within immunohistological subtypes, all the primary tumours regardless of immunohistological subtypes exhibited significant upregulation in gonadotrophin-releasing hormone (GnRH) pathways. Further, upon differential gene expression across tumours within p53 mutation statuses, HSPA1A (chaperone Hsp70) showed significantly lower expression in wild p53-negative (p53-) tumours compared to mutated p53-positive (p53+) tumours.In examining the differential expression in tumours across EMT characteristics, in CTC-positive (CTC+) tumours, various viral oncogenes like Epstein-Barr Virus, hepatitis B, and Kaposi-Sarcoma Associated Herpes Virus were upregulated. Overall present finding strives to identify unique molecular signatures for each breast cancer subtype/class providing a primary insight into identifying potential prognostic markers, particularly within the Caucasian demographic.