Discovery of Novel Hub Genes Across Breast, Ovarian, and Prostate Cancers

Chandler, Stephen (2022). Discovery of Novel Hub Genes Across Breast, Ovarian, and Prostate Cancers. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00014bce

Abstract

Breast, ovarian, and prostate cancers are amongst the most prevalent diagnosed cancers annually. These cancers are classified into subtypes based on specific characteristics, however, there are some common underlying aetiological features such as hormone receptors. Few studies have investigated such common features. Here, breast, ovarian and prostate cancers were analysed to identify cross-cancer gene/s that could potentially be used as biomarkers and/or treatment targets. A novel method/workflow using R programming was developed to integrate publicly available microarray tissue (RNA) data to increase sensitivity/sample numbers.

Significantly upregulated differentially expressed genes (DEGs) that were identified, were compared between the three cancers using classifications identified in literature. Two analyses were conducted comparing subtypes: 1) histological breast cancer, ovarian cancer tissue location, and prostate cancer Gleason grade group; 2) breast cancer molecular, ovarian epithelial, and prostate cancer Gleason score. Three cross-cancer significantly upregulated DEGs, HMMR, CENPE, and STIL were identified in both analyses: 1) HMMR Log2FC = 1.37 (P = 1.29E-10), CENPE Log2FC = 1.12 (P = 6.62E-08), and STIL Log2FC = 1.07 (P = 4.38E-08); 2) HMMR Log2FC = 1.64 (P = 2.23E-04), CENPE Log2FC = 1.42 (P = 5.82E-05), STIL Log2FC = 1.35 (P = 7.82E-06).

HMMR, CENPE, and STIL were significantly associated with reduced survival times (using 95% confidence interval) in recurrence free survival (Hazard Ratio (HR) = 1.18 - 1.84, P = 1E-16 - 0.012), and in overall survival (HR = 1.29 - 2.10, P = 7.1E-03 - 5.2E-09).

Network analysis identified HMMR, CENPE, and STIL as hub genes. Gene ontology (GO) and literature search identified them as functioning in G2/M phase cell cycle transition, indicating a shared mechanism/s of action. Therefore, the hub genes (HMMR, CENPE, STIL) termed ‘HCS three-gene signature’ were identified as potential biomarkers and treatment targets in breast, ovarian, or prostate cancers, regardless of subtype.

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