High Expression of C8orf76 Is an Independent Predictive Factor of Poor Prognosis in Patients with Breast Cancer.

Abstract

C8orf76 is a nuclear protein-encoding gene highly expressed in gastric tumor tissues that contributes to poor overall survival (OS). However, its function in breast cancer is unknown. We used The Cancer Genome Atlas (TCGA) database to investigate the role of C8orf76 in breast cancer. We used logistic regression to estimate the relationship between C8orf76 and clinical-pathological features, followed by Kaplan-Meier and Cox regression analyses to assess the prognostic value of the gene regarding survival of patients with breast cancer from TCGA database. To explore the biological functions of C8orf76, gene ontology (GO), Kyoto Genome Encyclopedia (KEGG) enrichment analysis, and gene set enrichment analysis (GSEA) were used. We established a nomogram for high or low C8orf76 expression in breast cancer patients based on Cox multivariate analysis. Finally, we verified the proliferation-promoting effect of C8orf76 on breast cancer cells with CCK8 kit and further explored its role of apoptosis by flow cytometry. High C8orf76 expression was observed in breast cancer tissues and significantly correlated with clinical stage. Kaplan-Meier survival analysis showed that elevated C8orf76 expression was associated with poor OS. Among the highly expressed C8orf76 phenotypes, GO and KEGG analysis showed significant enrichment in aromatase activity and PPAR signaling pathway, whereas GSEA showed differential enrichment in receptor tyrosine signaling, PI3K/AKT signaling pathway, and some data sets in extracellular matrix and adhesion. Lower expression of C8orf76 leads to reduced proliferation, increased apoptosis, and downregulation of pAKT and Bcl-2 in breast cancer cells. High C8orf76 expression may be a valuable biomarker related to the diagnosis and prognosis of patients with breast cancer.