Background: Recent discoveries indicate that the enzyme fatty acid 2-hydroxylase (FA2H) is associated with biological behavior and can be used for outcome prediction in several types of cancers. Such relevancy, however, between FA2H and ovarian cancer is not clear. Therefore, we carried out this study to compare the expression of FA2H with the clinicopathological features of ovarian cancer. Methods: Using the Oncomine database, we examined the expression levels of the FA2H gene in ovarian cancer tissues and their adjacent noncancerous tissues that had been evaluated by quantitative reverse-transcription polymerase chain reaction (PCR) analyses. We performed Kaplan-Meier curve analyses for overall survival and progression-free survival. In addition, relationships between the FA2H expression levels and clinicopathological features of ovarian cancer were analyzed. Finally, FA2H small interfering RNAs (siRNAs) or negative control siRNAs were separately transfected into OVCAR-3 and SKOV-3 cells to explore the downstream effects. From these results, Gli1 expression was tested by real-time PCR, and the effects of FA2H expression levels on the sensitivity of ovarian cancer cells to cisplatin chemotherapy was evaluated using sulforhodamine B assays. Results: Compared with the adjacent tissues, FA2H was expressed at lower levels in the ovarian cancer tissues. In survival analyses, decreased FA2H was significantly associated with poorer survival outcome in multiple subtypes of ovarian cancer. In addition, FA2H expression was significantly associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage, differentiation, lymph node involvement, tumor size, ascites, CA125 levels, and pelvic involvement. Knockdown of FA2H expression by siRNAs in the OVCAR-3 and SKOV-3 cell lines reduced their sensitivity to cisplatin, via modulation of GLI Family Zinc Finger 1 (Gli1) gene expression. Conclusion: Our results demonstrate that FA2H is a biomarker for ovarian cancer and it may serve as a useful prognostic factor.
Keywords: Gli1; chemotherapy; cisplatin; fatty acid 2-hydroxylase; ovarian cancer.