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Research Article
Open Access

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 and JAE-HOON KIM
Cancer Genomics & Proteomics November 2019, 16 (6) 553-562; DOI: https://doi.org/10.21873/cgp.20157
GWAN HEE HAN
1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea
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DOO BYUNG CHAY
1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea
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JOO MI YI
2Department of Microbiology and Immunology, Inje University College of Medicine, Busan, Republic of Korea
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HANBYOUL CHO
1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, 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.
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  • For correspondence: hanbyoul@yuhs.ac
JOON-YONG CHUNG
3Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
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JAE-HOON KIM
1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea
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    Figure 1.

    USP10 and p14ARF expression in formalin-embedded normal, benign, borderline, and EOC tissues. Both USP10 and p14ARF proteins were expressed in cytoplasm. (A) Representative immunohistochemical image of USP10 and p14ARF in normal, benign, borderline, and EOC tissues. Scale bar: 250 μm. (B) IHC staining score of USP10 and p14ARF depended on diagnostic category, FIGO stage, and tumour grade.

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    Figure 2.

    Spearman's rank correlation analysis between USP10 and p14ARF expression. There was a significant positive correlation between USP10 and p14ARF expression in EOCs.

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    Figure 3.

    Kaplan–Meier survival curves of USP10 and p14ARF expression in EOC. (A) EOC with negative USP10 expression exhibited poor DFS compared to USP10-positive groups (p<0.001). EOC with negative p14ARF expression exhibited poor DFS compared to p14ARF-positive group (p<0.033). When expression of both USP10 and p14ARF was negative, poor DFS was observed compared to the group positive for both USP10 and p14ARF (p<0.001). (B) When USP10 was not detected in EOCs, poor OS was observed compared to the USP10-positive group (p<0.001). The group in which neither USP10 nor p14ARF were expressed, poor OS was observed compared to the group positive for both USP10 and p14ARF (p<0.001).

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    Figure 4.

    The CpG island located in the USP10 and p14ARF promoter regions were analyzed by bisulphite sequencing. A schematic representation of USP10 or p14ARF CpG island is shown on the top. The red bar below CpG island represents the regions analysed by bisulphite sequencing. Vertical lines indicate each CpG site. Bisulphite sequencing analysis was performed for the (A) USP10 and (B) p14ARF genes in representative EOC (n=5) and normal (n=5) samples. Each circle represents a CpG dinucleotide. Black circles represent methylated cytosine while white circles represent unmethylated cytosines. TSS: Transcription start site; EOC: epithelial ovarian cancer.

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Cancer Genomics - Proteomics: 16 (6)
Cancer Genomics & Proteomics
Vol. 16, Issue 6
November-December 2019
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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
Cancer Genomics & Proteomics Nov 2019, 16 (6) 553-562; DOI: 10.21873/cgp.20157

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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
Cancer Genomics & Proteomics Nov 2019, 16 (6) 553-562; DOI: 10.21873/cgp.20157
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Keywords

  • Epithelial ovarian cancer
  • tumor marker
  • USP10
  • p14ARF
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