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Serum KIAA1199 Is a Surrogate Marker for Epithelial-Mesenchymal Transition that Predicts the Postoperative Metastasis and Prognosis of Cholangiocarcinoma
39 Pages Posted: 27 Jun 2019
More...Abstract
Background: Numerous studies have shown that KIAA1199 (CEMIP) acts as an oncoprotein in many digestive system tumors. However, the role and potential molecular mechanisms of KIAA1199 in the progression of cholangiocarcinoma (CCA) remain unclear.
Methods: Immunohistochemical staining, Western blotting and Quantitative real-time PCR (qRT-PCR) were used to detect the expression of KIAA1199 in human CCA and adjacent nontumor tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of KIAA1199 in serum and bile. The effect of KIAA1199 on proliferation and metastasis was evaluated by functional assays in vitro. Proteins associated with epithelial-mesenchymal transition (EMT) and the activation of the relevant signaling pathways were measured using Western blotting.
Key findings: KIAA1199 was upregulated in clinical CCA tissues and cell lines compared to paired paracancerous tissues or normal cholangitic epithelial cells. As a secreted protein, KIAA1199 can also be detected in serum and bile. In vitro, KIAA1199 overexpression (OE) promoted CCA growth and metastasis and induced EMT, and the silencing of KIAA1199 had the opposite effect. Moreover, through the analysis of clinical data from 177 patients' tumor tissues, 41 patients' serum and 20 patients' bile supernatant, we found that high levels of KIAA1199 correlated with postoperative metastasis, especially with prognosis in CCA.
Conclusion: In the clinical setting, KIAA1199 is a promising new diagnostic molecule and therapeutic target for CCA.
Funding Statement: This study is supported by the National Natural Science Foundation of China (NO. 81571367), Key R & D project of Shandong Province (NO.2017GSF218021).
Declaration of Interests: The author reports no conflicts of interest in this work.
Ethics Approval Statement: This study was approved by the Research Ethics Committee of Qilu Hospital of Shandong University.
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