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Peer-reviewedCC BY-NC-ND 4.0Diagnostic Pathology

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

  1. 1Department of Biochemistry and Molecular Biology, the Key Laboratory of Neurobiology and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China
  2. 2Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  3. 3Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, China

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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BibTeX
@article{hou2026expression,
  title = {{Expression, association with clinicopathological features and prognostic potential of FOXR2, mTOR, HIF−1α and PKM2 in high−grade serous carcinoma of the ovary}},
  author = {Lianguo Hou and Xinyi Dong and Min Li and Jiaxi Yang and Xueli Guo and Juan Wang and Jun Zhang},
  journal = {Diagnostic Pathology},
  year = {2026},
  month = aug,
  doi = {10.1186/s13000-026-01818-3},
  url = {https://doi.org/10.1186/s13000-026-01818-3},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Expression, association with clinicopathological features and prognostic potential of FOXR2, mTOR, HIF−1α and PKM2 in high−grade serous carcinoma of the ovary
AU  - Lianguo Hou
AU  - Xinyi Dong
AU  - Min Li
AU  - Jiaxi Yang
AU  - Xueli Guo
AU  - Juan Wang
AU  - Jun Zhang
PY  - 2026
DA  - 2026/08/08
JO  - Diagnostic Pathology
DO  - 10.1186/s13000-026-01818-3
UR  - https://doi.org/10.1186/s13000-026-01818-3
AB  - Background: 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.  Methods: 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.  Results: 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.  Conclusions: 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.
SN  - 1746-1596
ER  -