Wu Zhengchun, Liu Rushi, Miao Xiongying, Li Daiqiang, Zou Qiong, Yuan Yuan, Yang Zhulin
Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
School of Medicine. Hunan Normal University, Changsha, Hunan 410013, China.
J Cancer. 2020 Jan 1;11(1):199-207. doi: 10.7150/jca.36886. eCollection 2020.
Some studies have demonstrated that Hapto and Gremlin1 play an important biological role in many neoplasms. However, the role of Hapto and Gremlin1 in extrahepatic cholangiocarcinoma (ECC) remains to be revealed. Thus, this study investigated the prognostic and clinicopathological significance of Hapto and Gremlin1 expression in ECC. We examined Hapto and Gremlin1 expression in 100 ECC, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues using EnVision immunohistochemistry. The relationship between Hapto and Gremlin 1 expression and clinicopathological parameters was evaluated using the χ test or Fisher's exact test. The overall survival of patients was analyzed using Kaplan-Meier univariate survival analysis and log-rank tests. Hapto and Gremlin1 proteins were overexpressed in ECC compared to peritumoral tissues, adenoma, and normal biliary tract (<0.05 or <0.01). The positive rate of Hapto and Gremlin1 expression was significantly higher in cases with poor differentiation, lymph node metastasis, invasion of surrounding tissues and organs, a tumor-node-metastasis (TNM) stage of III or IV and no resection. Kaplan-Meier survival analysis showed that ECC patients with positive Hapto and/or Gremlin1 expression survived significantly shorter than patients with negative Hapto and/or Gremlin1 expression. Cox multivariate analysis revealed that positive Hapto and Gremlin1 expression were independent poor prognostic factors in ECC patients. The present study indicated that positive Hapto and/or Gremlin1 expression are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in ECC.
一些研究表明，Hapto和Gremlin1在许多肿瘤中发挥着重要的生物学作用。然而，Hapto和Gremlin1在肝外胆管癌（ECC）中的作用仍有待揭示。因此，本研究探讨了Hapto和Gremlin1表达在ECC中的预后及临床病理意义。我们采用EnVision免疫组织化学法检测了100例ECC、30例癌旁组织、10例腺瘤和15例正常胆管组织中Hapto和Gremlin1的表达。采用χ检验或Fisher精确检验评估Hapto和Gremlin 1表达与临床病理参数之间的关系。采用Kaplan-Meier单因素生存分析和对数秩检验分析患者的总生存期。与癌旁组织、腺瘤和正常胆管相比，ECC中Hapto和Gremlin1蛋白表达上调（<0.05或<0.01）。在分化差、有淋巴结转移、侵犯周围组织和器官、肿瘤-淋巴结-转移（TNM）分期为III或IV期以及未行切除的病例中，Hapto和Gremlin1表达的阳性率显著更高。Kaplan-Meier生存分析显示，Hapto和/或Gremlin1表达阳性的ECC患者的生存期明显短于Hapto和/或Gremlin1表达阴性的患者。Cox多因素分析显示，Hapto和Gremlin1表达阳性是ECC患者独立的不良预后因素。本研究表明，Hapto和/或Gremlin1表达阳性与ECC的发病机制、临床、病理和生物学行为以及不良预后密切相关。
