Expression, association with clinicopathological features and prognostic potential of FOXR2, mTOR, HIF−1α and PKM2 in high−grade serous carcinoma of the ovary

High−grade serous carcinoma (HGSC) of the ovary is the most common and deadly subtype of gynecological malignancy. More and more studies have shown that Forkhead Box R2 (FOXR2) is a carcinogenic driver that can enhance cell growth and tumor formation. However, the role of FOXR2 in the development of HGSC and its underlying molecular mechanisms remain unclear. This study investigated the role of FOXR2 in HGSC progression and its relationship with glycometabolic reprogramming, specifically the mTOR/HIF−1α signaling pathway and its downstream key glycolytic enzyme, PKM2. Immunohistochemistry for FOXR2, mTOR, HIF−1α and PKM2 was performed on formalin−fixed paraffin−embedded HGSC tissue and normal fallopian tube tissue. Kaplan Meier analysis and Cox proportional hazards regression analysis were used to evaluate the overall survival curve and independent prognostic factors. In the present study, FOXR2, mTOR, HIF−1α and PKM2 proteins are highly expressed in HGSC, and are positively correlated with FIGO stage of ovarian cancer. In addition, these four proteins were positively correlated with each other. Overall survival analysis showed that the expression levels of FOXR2, mTOR, HIF−1α and PKM2 proteins, as well as FIGO stage, were correlated with patient prognosis. In addition, FIGO staging was an independent prognostic factor affecting the poor prognosis of patients. Taken together, the present results suggested that FOXR2, mTOR, HIF−1α and PKM2 have crucial roles in the progression and prognosis of HGSC and may be potential therapeutic targets.