Ferroptosis, DNA damage repair, and transporter proteins: associated with platinum sensitivity and prognosis in epithelial ovarian cancer.

OBJECTIVE: This study aimed to links between ATP7B, CTR1, GPX4, 53BP1, p-H2AX and p-ATM expression, platinum sensitivity and prognosis in patients with epithelial ovarian cancer (EOC).

METHODS: This study integrated clinical research, in vitro experiments, and database analysis, incorporating immunohistochemistry (IHC) of EOC tissues and survival analyses based on Kaplan-Meier and Cox regression models, expression differences of proteins in platinum-sensitive and platinum-resistant ovarian cancer cell lines, as well as cross-validation utilizing public transcriptome databases.

RESULTS: Patients with EOC with high expression levels of CTR1, 53BP1, and p-H2AX, and low expression levels of ATP7B, GPX4, and p-ATM exhibited increased sensitivity to platinum-based chemotherapeutic agents, whereas those with high protein expression levels of CTR1, 53BP1, and p-H2AX, and low expression levels of GPX4, exhibited longer overall survival. However, the protein levels of p-ATM and ATP7B were not significantly correlated with the prognosis of EOC. Analysis of the KM-pPlotter database indicated revealed that high mRNA levels of CTR1 and H2AX, coupled with low mRNA levels of GPX4 and ATM, were associated with a better prognosis; however, the mRNA levels of 53BP1 and ATP7B were not significantly correlated with prognosis of EOC.

CONCLUSIONS: High expression levels of CTR1, 53BP1, and p-H2AX, along with low expression levels of ATP7B, GPX4, and p-ATM, may be associated with platinum sensitivity in patients with EOC. Furthermore, the protein expression levels of 53BP1, H2AX, CTR1, and GPX4 may be correlated with survival rate in patients with EOC and prognosis of EOC.