Systems biology-driven identification of biomarkers and significant pathways in radiation-induced hormone-sensitive...

Radiation-induced damage to nucleic acid and other important cellular constituents could likely cause cancer. The present study has analyzed mutated genes with dysregulated expression signatures due to radiation. We have predicted biomarkers specific to hormone-sensitive cancers (HSCs) namely breast cancer (BC), prostate cancer (PC), ovarian cancer (OC), and endometrial cancer (EC). The study has also attempted to prospect the pathways associated with HSCs and radiation exposure through network analysis and functional enrichment analysis. An overlap of important cell cycle pathways, DNA binding, and transcription activity pathways were found in comparison with HSCs and the radiation hallmark pathways. Hub genes TNF, STAT3, CTNNB1, and MYC in BC; IL1B, CTNNB1, ESR1, and SRC in PC; CTNNB1, BRCA1, JUN, and KRAS in OC; PIK3CA, PTEN, and ESR1 in EC were found as hypoxic signatures due to radiation. Further, the expression survival analysis found MYC and STAT3 in BC, CTNNB1 in PC, JUN, and BRCA1 in OC, and ESR1 in EC were significantly dysregulated and further mutational profiling validated MYC with 18%, STAT3 with 2.6%, and all other genes with 4% mutation. Thus, these genes are proposed as radiation-sensitive diagnostic biomarkers in HSCs.