Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer

Abstract

Background Ovarian cancer has greatly endangered and deteriorated female health conditions worldwide. Refinement of predictive biomarkers could enable patient stratification and help optimize disease management. Methods RAD51 expression profile, target-disease associations, and fitness scores of RAD51 were analyzed in ovarian cancer using bioinformatic analysis. To further identify its role, gene enrichment analysis was performed, and a regulatory network was constructed. Survival analysis and drug sensitivity assay were performed to evaluate the effect of RAD51 expression on ovarian cancer prognosis. The predictive value of RAD51 was then confirmed in a validation cohort immunohistochemically. Results Ovarian cancer expressed more RAD51 than normal ovary. RAD51 conferred ovarian cancer dependency and was associated with ovarian cancer. RAD51 had extensive target-disease associations with various diseases, including ovarian cancer. Genes that correlate with and interact with RAD51 were involved in DNA damage repair and drug responsiveness. High RAD51 expression indicated unfavorable survival outcomes and resistance to platinum, taxane, and PARP inhibitors in ovarian cancer. In the validation cohort (126 patients), high RAD51 expression indicated platinum resistance, and platinum-resistant patients expressed more RAD51. Patients with high RAD51 expression had shorter OS (HR = 2.968, P < 0.0001) and poorer PFS (HR = 2.838, P < 0.0001). RAD51 expression level was negatively correlated with patients’ survival length. Conclusions Ovarian cancer had pronounced RAD51 expression and RAD51 conferred ovarian cancer dependency. High RAD51 expression indicated poor survival and decreased drug sensitivity. RAD51 has predictive value in ovarian cancer and can be exploited as a predictive biomarker.

CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression

“…A previous study reported that CTBP1 expression influences DDP resistance of breast cancer cells by activating RAD51 expression ( 19 ). In the present study, RT-qPCR and western blot analysis were used to evaluate the expression of RAD51 in the aforementioned five cell lines.…”

“…In addition, it has been suggested that inhibition of RAD51 enhances the therapeutic effect of DDP on gastric cancer ( 34 ). Furthermore, CTBP1 influences the DDP resistance of breast cancer cells by activating RAD51 expression ( 19 ). The results of the present study demonstrated that CTBP1 expression was upregulated in DDP-resistant AGS/DDP and HGC-27/DDP gastric cancer cells.…”

“…DNA repair protein RAD51 homolog 1 (RAD51) is a protein associated with DNA damage repair ( 18 ). However, RAD51 expression is also associated with the development of different types of cancer, such as ovarian, colorectal and breast cancer ( 19 – 21 ). STAT5A/B inhibition increases the sensitivity of prostate cancer cells to radiotherapy through inhibition of RAD51 and DNA repair ( 22 ).…”

KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer

“…Feng Y et al. reported that high RAD51 expression indicated unfavourable survival outcomes and resistance to platinum, taxane, and PARP inhibitors in patients with ovarian cancer [38] . These results are consistent with our study.…”

Protein expression profiling identifies a prognostic model for ovarian cancer

“…However, they cannot fully reflect tumor biological characteristics, and individual differences lead to inadequate specificity and incompetence [4,5]. In the past few decades, the rapid and prosperous development of sequencing technology has provided opportunities to systematically explore tumors, and a myriad of genes including RAD51 and PAWR were explored as predictive biomarkers in ovarian cancer [5,7,8]. Due to the intratumor heterogeneity of this deadly disease and the complex molecular mechanisms affecting its prognosis, single factor prediction models usually have low accuracy and efficacy [4,5].…”