Loss of Both USP10 and p14ARF protein expression is an independent prognostic biomarker for poor prognosis in patients with epithelial ovarian cancer

Gwan Hee Han, Doo Byung Chay, Joo Mi Yi, Hanbyoul Cho, Joon Yong Chung, Jae Hoon Kim

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13 Citations (Scopus)

Abstract

Background/Aim: The prognostic role of USP10 in epithelial ovarian cancer has been studied in various human cancers. Our aim was to evaluate the clinical and pathological significance of USP10 in epithelial ovarian cancer. Materials and Methods: Immunohistochemical analyses of the expression of USP10 and p14ARF by using tissue microarrays were performed in 336 ovarian tumours and the data were compared with clinicopathological variables. We examined their level of DNA methylation around the putative transcriptional start site in 5' CpG islands in fresh frozen tissues and ovarian cancer cells. Results: Expression of USP10 and p14ARF was significantly lower in cancer tissues than in normal epithelium. Low USP10 expression and a combined USP10/p14ARF low expression were revealed to be independent prognostic factors. A high degree of methylation in USP10 and p14ARF CpG islands was found by methylation specific PCR analysis in cancer than in normal tissues and cells. Conclusion: Decreased expression of USP10 or combined USP10/p14ARF decreased expression is a strong indicator of poor prognosis in patients with ovarian cancer.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalCancer Genomics and Proteomics
Volume16
Issue number6
Publication statusPublished - 2019

Bibliographical note

Funding Information:
1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Microbiology and Immunology, Inje University College of Medicine, Busan, Republic of Korea; 3Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.

Funding Information:
57 borderline ovarian tumours, 153 benign epithelial ovarian tumours, and 79 nonadjacent normal epithelial tissues were included in this study. The tumour specimens were gathered from patients who underwent primary surgery at Gangnam Severance Hospital between 1996 and 2012. Some paraffin blocks were supplied by the Korea Gynecologic Cancer Bank under Bio & Medical Technology Development Program of the Ministry of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9B8069610). All tumour tissues were histologically examined and only the specimens with a sufficient proportion of tumour cells were selected for tissue microarray (TMA) construction. Tumour staging was performed by the International Federation of Gynecology and Obstetrics (FIGO) classification. Clinical data including age at diagnosis, surgical procedure, survival period, and survival status were collected by reviewing medical records. Response to therapy was monitored according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) by computed tomography (15). Tumour grades and cell types were collected from the pathology report. All biological samples were acquired following informed consent from patients based on institutional review board (IRB) guidelines.

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9 B8069610). Funding. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Publisher Copyright:
© 2019 International Institute of Anticancer Research. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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