J Cancer 2016; 7(6):722-729. doi:10.7150/jca.14277

Research Paper

Identification of Cathepsin K in the Peritoneal Metastasis of Ovarian Carcinoma Using In-silico, Gene Expression Analysis

Haiming Xu1*, Yu Ma 2*, Yan Zhang2, 3, Zimin Pan4, Yan Lu4,5, Pengyuan Liu5, Bingjian Lu6✉

1. Institute of Bioinformatics, School of Agriculture & Biological Technology, Zhejiang University, Hangzhou, Zhejiang, China.
2. Department of Clinical Laboratory, 4Gynecologic Oncology, 6Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
3. Department of Clinical Laboratory, Yiwu Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
4. Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
5. Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
6. Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
* Both authors contributed equally to this work.

Abstract

Ovarian carcinomas (OC) are often found in the advanced stage with wide peritoneal dissemination. Differentially-expressed genes (DEGs) between primary ovarian carcinoma (POC) and peritoneal metastatic ovarian carcinomas (PMOC) may have diagnostic and therapeutic values. In this study, we identified 246 DEGs by in-silico analysis using microarrays for 153 POCs and 57 PMOCs. Pathway analysis shows that many of these genes are associated with lipid metabolism. Microfluidic, card-based, quantitative PCR validated 19 DEGs in PMOCs versus POCs (p<0.05). Immunohistochemistry confirmed overexpression of MMP13, CTSK, FGF1 and GREM1 in PMOCs (p<0.05). ELISA detection indicated that serum CTSK levels were significantly increased in OCs versus controls (p<0.001). CTSK levels discriminated between OCs and healthy controls (ROC 0.739; range 0.685-0.793). Combining CA125 and HE4 with CTSK levels produced an improved specificity in the predictive of OCs (sensitivity 88.3%, specificity 92.0%, Youden's index 80.3%). Our study suggests that CTSK levels may be helpful in the diagnosis of primary, ovarian carcinoma.

Keywords: ovarian carcinoma, metastasis, microarray, CTSK (cathepsin K).

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How to cite this article:
Xu H, Ma Y, Zhang Y, Pan Z, Lu Y, Liu P, Lu B. Identification of Cathepsin K in the Peritoneal Metastasis of Ovarian Carcinoma Using In-silico, Gene Expression Analysis. J Cancer 2016; 7(6):722-729. doi:10.7150/jca.14277. Available from http://www.jcancer.org/v07p0722.htm