Prognostic and clinicopathological significance of Hapto and Gremlin1 expression in extrahepatic cholangiocarcinoma

Background: 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. Methods: 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 χ2 test or Fisher's exact test. The overall survival of patients was analyzed using Kaplan-Meier univariate survival analysis and log-rank tests. Results: Hapto and Gremlin1 proteins were overexpressed in ECC compared to peritumoral tissues, adenoma, and normal biliary tract (P<0.05 or P<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. Conclusion: 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.