Identification of endoplasmic reticulum stress-related gene signature reveals KRT8 as a target in ovarian cancer ï¿¿

Abstract

Purpose: Ovarian cancer (OC) is an invasive gynecological cancer with an overall 5-year survival rate less than 45%. Endoplasmic reticulum (ER) stress influence oncogenic events and immune-regulatory programmers to dictate malignant progression, antitumor immunity and response to treatment. However, endoplasmic reticulumstress (ERS) in ovarian cancer is not fully understood and needs further study. Methods: The RNA-sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). We screened ER stress-related genes associated with ovarian tumor prognosis and developed an ER stress risk score model by LASSO regression. We used the ER stress risk score as the entry point to explore differences in the infiltration rate of immune cells. Subsequently, biological role and expression of risk gene KRT8 was validated base on molecular biology experiment. Results: We identified 573 genes related to ER stress that were differentially expressed genes (DEGs) between normal and tumor tissues. ER stress-related risk signature (ERRS) constructed using the TCGA dataset was regarded as an independent and significant prognostic model for predicting cancer progression and instructing clinical decisions. Additional KRT8 was overexpressed in ovarian cancer cells and tissues and downregulation of the KRT8 gene inhibited ovarian cancer cell proliferation and migration (in both SKOV3 and OVCAR8 cells) in vitro. Conclusion:The model constructed with ER stress-related genes could be used to evaluate the prognostic risk for OC patients. Notably, we discovered that KRT8 acts as a risk gene in ovarian cancer, promoting tumor progression, and is expected to be a novel therapeutic target.