Tang Zengwei, Yang Yuan, Zhang Jinduo, Fu Wenkang, Lin Yanyan, Su Gang, Li Yan, Meng Wenbo, Li Xun, Xie Xiaodong
The First Clinical Medical School of Lanzhou University, Lanzhou 730000, China.
Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.
J Cancer. 2019 Jul 5;10(17):3985-3999. doi: 10.7150/jca.29354. eCollection 2019.
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. 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). 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 ( = 0.030). The univariate analysis showed that tumor size ( = 0.002), vascular invasion ( = 0.001), histological grading ( = 0.011), and PPP3CA expression ( = 0.033) were statistically significant risk factors affecting the prognosis of CCA patients. The multivariate analysis demonstrated PPP3CA expression ( = 0.009) and vascular invasion ( = 0.012) were statistically significant independent risk factors of CCA patients. 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.
胆管癌（CCA）患者的预后较差，因为晚期诊断限制了手术治疗和根治性治疗方案的益处。本研究旨在筛选CCA患者的生物标志物。采用定量iTRAQ蛋白质组学分析来鉴定CCA组织和癌旁组织之间差异表达的蛋白质。我们使用免疫组织化学检测了CCA组织中PRDX2、BGN、LUM和PPP3CA的表达谱。我们进一步研究了PPP3CA表达与CCA患者（n = 91）生存之间的相关性。使用iTRAQ技术鉴定出2886种可信蛋白质，其中233种差异表达。PRDX2、BGN、PPP3CA和LUM在CCA组织中表达，而除LUM外，它们在胆总管囊肿组织中不表达。在91例CCA患者中，有22例（24.2%）的癌细胞胞质中表达PPP3CA。PPP3CA阳性表达的患者生存期明显短于未表达的患者（P = 0.030）。单因素分析显示，肿瘤大小（P = 0.002）、血管侵犯（P = 0.001）、组织学分级（P = 0.011）和PPP3CA表达（P = 0.033）是影响CCA患者预后的统计学显著危险因素。多因素分析表明，PPP3CA表达（P = 0.009）和血管侵犯（P = 0.012）是CCA患者统计学显著的独立危险因素。结果表明，PPP3CA在CCA患者中的表达是预后不良的一个新的独立因素，也是CCA患者有用的预后预测指标。
