Coexpression network analysis identified Krüppel-like factor 6 (KLF6) association with chemosensitivity in ovarian cancer.

Abstract

Although most patients with ovarian cancer (OC) are initially sensitive to paclitaxel/carboplatin combination chemotherapy, eventually they develop resistance to chemotherapy drugs and experience disease relapse. OC is the most lethal gynecological malignancy, and the five-year survival rate is extremely low. Thus, research on specific biomarkers and potential targets for chemotherapy-resistant patients with OC is needed. In our study, genes in the top 10% of variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues were determined to conduct a weighted gene coexpression network analysis (WGCNA). The magenta module was most strongly related to OC chemoresponse. Gene ontology enrichment analysis indicated that the function of the magenta module primarily focused on transcription regulation, cell cycle control, and apoptosis modulation. Integration of the WGCN with the protein-protein interaction network identified five candidate genes. These five genes were verified using the GSE51373 test set, and Krüppel-like factor 6 ( KLF6) was identified as tightly linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve showed that KLF6 differentiated chemoresistant from chemosensitive OC tissues. The Kaplan-Meier online database indicated that high KLF6 expression was associated with poor OC prognosis. Gene set enrichment analysis determined that the KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA-damage repair signaling pathways. In conclusion, KLF6 was identified in association with OC chemoresistance, and the mechanism of KLF6-mediated chemoresistance may involve the cell cycle, mTOR, and DNA-damage repair signaling pathways.