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

机译:用计算机模拟基因表达分析鉴定组织蛋白酶K在卵巢癌腹膜转移中的作用

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摘要

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.
机译:卵巢癌(OC)通常在晚期阶段通过广泛的腹膜扩散发现。原发性卵巢癌(POC)和腹膜转移性卵巢癌(PMOC)之间的差异表达基因(DEG)可能具有诊断和治疗价值。在这项研究中,我们通过计算机芯片分析使用微阵列对153个POC和57个PMOC确定了246个DEG。途径分析表明,这些基因中有许多与脂质代谢有关。微流控,基于卡的定量PCR验证了PMOC与POC中的19 DEG(p <0.05)。免疫组织化学证实了PMOCs中MMP13,CTSK,FGF1和GREM1的过度表达(p <0.05)。 ELISA检测表明,OCs中的血清CTSK水平显着高于对照组(p <0.001)。 OC和健康对照组之间的CTSK水平有所区别(ROC 0.739;范围0.685-0.793)。将CA125和HE4与CTSK水平结合使用可提高OC预测的特异性(敏感性88.3%,特异性92.0%,尤登指数80.3%)。我们的研究表明,CTSK水平可能有助于诊断原发性卵巢癌。

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