Discovery of candidate hub genes in breast cancer

Chandler, Stephen; Gangadharannambiar, Priyadarsini; Crea, Francesco; Hirst, Mark; Cox, Angela and Rigas, Sushila (2019). Discovery of candidate hub genes in breast cancer. In: New Developments in Breast Cancer Research - From the Lab to the Clinic, 2019 BACR Special Conference, 9-11 Oct 2019, The Sage, Newcastle Gateshead, UK.

Abstract

The functions of clinically relevant genes in breast cancer and their molecular role in cell pathways has not been completely discovered yet. Here we aimed to identify candidate hub genes in breast cancer that reduce survival and are confirmed in ovarian and prostate cancers, so we could select the most impactful genes. Using R scripting with Empirical Bayes Modified t-test we compared the gene expression levels of 436 normal tissues to 3,612 tumours with up to 13,000 genes from Caucasian microarray datasets in the Gene Expression Omnibus (NCBI). Seven novel candidate protein coding hub genes were identified. They were amongst the most significant (adjusted Benjamini-Hochberg FDR, P=1.20-3-8.76-11) and upregulated genes (log2 fold change=0.29-2.86), and correlated with overall survival (HR=2.12-4.95, P=0.01-0.04) in SurvExpress (omicX). We also constructed weighted gene co-expression network images using Cytoscape 3.7.1 (NIGMS) and identified corresponding cell pathways using The Gene Ontology knowledgebase and literature searches. So far, three of the candidate hub genes were linked in their cell pathways; mainly operating in mitotic spindle formation and the G2/M phase cell cycle check point, with one gene that may act to bypass the cell cycle checkpoint and apoptosis, and thereby allow uncontrolled proliferation. Next, we will analyse the functions of the remaining four candidate hub genes and propose a mechanism of action and validate these findings using siRNA assays. The discovery of novel candidate hub genes could be used to develop novel biomarkers and treatments for breast cancer that may also be applicable to ovarian and prostate cancers.

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