The Combination of Transient Receptor Potential Vanilloid Type 1 (TRPV1) and Phosphatase and Tension Homolog (PTEN) is an Effective Prognostic Biomarker in Cervical Cancer

Gwan Hee Han, Doo Byung Chay, Sanghee Nam, Hanbyoul Cho, Joon Yong Chung, Jae Hoon Kim

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7 Citations (Scopus)

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) has been reported to play an important role in human cancers. However, the knowledge about TRPV1 in cervical cancer is sparse. Therefore, we evaluated the expression and clinical significance of TRPV1 in cervical cancer. Immunohistochemical analyses were performed for TRPV1 and phosphatase and tension homolog (PTEN) to delineate clinical significance using 150 cervical cancers, 230 cervical intraepithelial neoplasias, and 312 normal cervical epithelial tissues in a tissue microarray. Furthermore, the role of TRPV1 in cell growth was assessed in a cervical cancer cell line. The TRPV1 expression was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasias, and normal epithelial tissues (P<0.001). In cervical cancer tissues, TRPV1 expression negatively correlated with PTEN expression (Spearman ρ=-0.121, P=0.009). Multivariate survival analysis revealed high TRPV1 expression (hazard ratio=3.41, 95% confidence interval: 1.25-9.27, P=0.016) as an independent prognostic factor for overall survival. Notably. the high TRPV1/low PTEN expression showed the highest hazard ratio (5.87; 95% confidence interval: 2.18-15.82, P<0.001) for overall survival. In vitro results demonstrated that the overexpression of TRPV1 was associated with increased cell viability and colony formation. Overexpression of TRPV1 could be a good biomarker for the prediction of chemoradiation response. Our result suggested promising potential of high TRPV1/low PTEN as prognostic and survival makers. The possible link between the biologic function of TRPV1 and PTEN in cervical cancer warrants further studies.

Original languageEnglish
Pages (from-to)214-223
Number of pages10
JournalInternational Journal of Gynecological Pathology
Volume40
Issue number3
DOIs
Publication statusPublished - 2021 May

Bibliographical note

Funding Information:
From the Department of Obstetrics and Gynecology, Yonsei University College of Medicine (G.H.H., D.B.C., H.C., J.H.K.); Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong (G.H.H.); Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (S.N.); and Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland (H.C., J.Y.C.). This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9B8069610). The authors declare no conflict of interest. Address correspondence to Hanbyoul Cho, MD, PhD, Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, Seoul 06273, South Korea. E-mail: hanbyoul@yuhs.ac.

Funding Information:
This study was conducted in a consecutive series of 150 patients with cervical cancer and 230 patients with cervical intraepithelial neoplasia (CIN) that underwent primary surgery at Gangnam Severance Hospital, Yonsei University College of Medicine, between 1996 and 2010. Some paraffin blocks were provided by the Korea Gynecologic Cancer Bank under the Bio & Medical Technology Development Program of the Ministry of the National Research Foundation (NRF) funded by the Korean government (MIST) (NRF-2017M3A9B8069610). All tumor tissues were histologically reviewed and the specimens presenting a sufficient number of tumor cells were included in the tissue microarray (TMA). The patients were clinically staged according to the FIGO staging system. Primary treatment for cervical cancer comprised type 3 radical hysterectomy with pelvic lymph node dissection. In the case of increased risk of relapse, including positive resection margins, positive lymph nodes, or parametrial invasion, platinum-based concurrent chemoradiation was added. Medical records were reviewed to obtain data including age, stage, surgical procedure, survival time, and survival status. Response to therapy was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) either with computed tomography or magnetic resonance imaging (16). Data on tumor size, cell type, tumor grade, and lymph node metastases were obtained from pathology reports. This study was approved by the Institutional Review Boards (IRBs) of Gangnam Severance Hospital.

Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Obstetrics and Gynaecology

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