Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, Xi'an 710061, China.
Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, Xi'an 710061, China.
Biomed Res Int. 2018 May 13;2018:6135016. doi: 10.1155/2018/6135016. eCollection 2018.
Hilar cholangiocarcinoma (HC) is a devastating malignancy that carries a poor overall prognosis. As a member of the AAA+ superfamily, Pontin becomes highly expressed in several malignant tumors, which contributes to tumor progression and influences tumor prognosis. In our research, Pontin expression in tumor specimens resected from 86 HC patients was detected by immunohistochemistry. Interestingly, high expression of Pontin was significantly associated with lymph node metastasis ( = 0.011) and tumor node metastasis (TNM) stage ( = 0.005). The Kaplan-Meier overall survival rate and multivariate analyses were performed to evaluate the prognosis of patients with HC. Patients with high Pontin expression had significantly poorer overall survival outcomes. Multivariate analyses found that Pontin was an independent prognostic factor ( = 0.001). Moreover, bioinformatics analysis confirmed the increase in Pontin mRNA expression levels in cholangiocarcinoma tissues. In addition, in vitro experiments showed that Pontin expression was inhibited at the mRNA as well as protein levels after transfection with Pontin siRNA in human cholangiocarcinoma cell lines. Moreover, significant suppression of cell invasion was observed after the downregulation of Pontin. Taken together, the present study suggested that Pontin could act as a potential prognostic predictor, which might be a new valuable molecular candidate for the prevention and treatment of HC.
肝门部胆管癌(HC)是一种预后极差的恶性肿瘤。作为 AAA+ 超家族的一员,Pontin 在多种恶性肿瘤中高表达,促进肿瘤进展并影响肿瘤预后。在我们的研究中,通过免疫组织化学检测了 86 例 HC 患者肿瘤标本中 Pontin 的表达。有趣的是,Pontin 的高表达与淋巴结转移( = 0.011)和肿瘤淋巴结转移(TNM)分期( = 0.005)显著相关。通过 Kaplan-Meier 总体生存率和多因素分析评估了 HC 患者的预后。Pontin 高表达的患者总体生存率显著降低。多因素分析发现 Pontin 是独立的预后因素( = 0.001)。此外,生物信息学分析证实了胆管癌组织中 Pontin mRNA 表达水平的增加。此外,在体外实验中,用人胆管癌细胞系转染 Pontin siRNA 后,Pontin 在 mRNA 和蛋白水平的表达均受到抑制。下调 Pontin 后,细胞侵袭明显受到抑制。综上所述,本研究表明 Pontin 可作为潜在的预后预测因子,可能成为预防和治疗 HC 的新的有价值的分子候选物。