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

Xu H, Ma Y, Zhang Y, Pan Z, Lu Y, Liu P, Lu B - J Cancer (2016)

Bottom Line: Pathway analysis shows that many of these genes are associated with lipid metabolism.Immunohistochemistry confirmed overexpression of MMP13, CTSK, FGF1 and GREM1 in PMOCs (p<0.05).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%).

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Bioinformatics, School of Agriculture & Biological Technology, Zhejiang University, Hangzhou, Zhejiang, China.

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.

No MeSH data available.


Related in: MedlinePlus

ROC curves of serum CTSK, MMP13, FGF1, CA125 and HE4 in the discrimination of OCs from normal healthy women.
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Figure 3: ROC curves of serum CTSK, MMP13, FGF1, CA125 and HE4 in the discrimination of OCs from normal healthy women.

Mentions: Figure 3 shows a receiver operating characteristic (ROC) curve of these serum biomarkers for the discrimination of OCs from healthy controls. The relative parameters including area under ROC (AUC) and Youden's index are given in Table 3. The established cutoff values of serum CA125, HE4 and CTSK predicted 22/32, 7/32, and 18/32 ovarian borderline tumors, respectively. We then defined the levels in any 2 of the 3 biomarkers over the cutoff values as the discriminator. This combination approach did not significantly improve the prediction of OCs, but improved its specificity (area under the AUC: 0.901; sensitivity 88.3%, specificity 92.0%, Youden's index 80.3%).


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

Xu H, Ma Y, Zhang Y, Pan Z, Lu Y, Liu P, Lu B - J Cancer (2016)

ROC curves of serum CTSK, MMP13, FGF1, CA125 and HE4 in the discrimination of OCs from normal healthy women.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4829559&req=5

Figure 3: ROC curves of serum CTSK, MMP13, FGF1, CA125 and HE4 in the discrimination of OCs from normal healthy women.
Mentions: Figure 3 shows a receiver operating characteristic (ROC) curve of these serum biomarkers for the discrimination of OCs from healthy controls. The relative parameters including area under ROC (AUC) and Youden's index are given in Table 3. The established cutoff values of serum CA125, HE4 and CTSK predicted 22/32, 7/32, and 18/32 ovarian borderline tumors, respectively. We then defined the levels in any 2 of the 3 biomarkers over the cutoff values as the discriminator. This combination approach did not significantly improve the prediction of OCs, but improved its specificity (area under the AUC: 0.901; sensitivity 88.3%, specificity 92.0%, Youden's index 80.3%).

Bottom Line: Pathway analysis shows that many of these genes are associated with lipid metabolism.Immunohistochemistry confirmed overexpression of MMP13, CTSK, FGF1 and GREM1 in PMOCs (p<0.05).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%).

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Bioinformatics, School of Agriculture & Biological Technology, Zhejiang University, Hangzhou, Zhejiang, China.

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.

No MeSH data available.


Related in: MedlinePlus