J Cancer 2019; 10(17):3985-3999. doi:10.7150/jca.29354 This issue

Research Paper

Quantitative Proteomic Analysis and Evaluation of the Potential Prognostic Biomarkers in Cholangiocarcinoma

Zengwei Tang1*, Yuan Yang1*, Jinduo Zhang1,2, Wenkang Fu1, Yanyan Lin2, Gang Su3, Yan Li4, Wenbo Meng1,2✉, Xun Li1,5, Xiaodong Xie3✉

1. The First Clinical Medical School of Lanzhou University, Lanzhou 730000, China.
2. Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.
3. School of Basic Medical Sciences, Institute of Genetics, Lanzhou University, Lanzhou 730000, China.
4. Cleveland Clinic, Department of Inflammation and Immunity, Cleveland OHIO 44195, USA.
5. The second department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.
* These authors contributed equally to this work.

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Citation:
Tang Z, Yang Y, Zhang J, Fu W, Lin Y, Su G, Li Y, Meng W, Li X, Xie X. Quantitative Proteomic Analysis and Evaluation of the Potential Prognostic Biomarkers in Cholangiocarcinoma. J Cancer 2019; 10(17):3985-3999. doi:10.7150/jca.29354. Available from https://www.jcancer.org/v10p3985.htm

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Abstract

Background & Aims: Cholangiocarcinoma (CCA) patients have poor outcomes since the late diagnosis limits the benefits of surgery therapy and curative treatment options. The present study was designed to screen the biomarkers for CCA patients.

Methods: Quantitative iTRAQ proteomic analysis was used to identify differentially expressed proteins between CCA and pericarcineous tissue. We examined the expression profile of PRDX2, BGN, LUM, and PPP3CA in CCA tissue using immunohistochemistry. We further investigated the correlation between PPP3CA expression and the survival of CCA patients (n=91).

Results: 2,886 confidential proteins were identified by using the iTRAQ technique, 233 of which were differentially expressed. PRDX2, BGN, PPP3CA, and LUM were expressed in CCA tissue, whereas they were not expressed in choledocal cyst tissue except for LUM. PPP3CA was expressed in the cytoplasm of carcinoma cells in 22 cases (24.2%) of 91 CCA patients. Patients with PPP3CA-positive expression showed a significantly shorter survival period than did non-expressing patients (P = 0.030). The univariate analysis showed that tumor size (P = 0.002), vascular invasion (P = 0.001), histological grading (P = 0.011), and PPP3CA expression (P = 0.033) were statistically significant risk factors affecting the prognosis of CCA patients. The multivariate analysis demonstrated PPP3CA expression (P = 0.009) and vascular invasion (P = 0.012) were statistically significant independent risk factors of CCA patients.

Conclusions: The results suggested that the expression of PPP3CA in CCA patients is a new independent factor for poor prognosis and a useful prognostic predictor for patients with CCA.

Keywords: cholangiocarcinoma, iTRAQ, PPP3CA, prognosis, bioinformarics