LRRK2 Is Associated with Recurrence-Free Survival in Intrahepatic Cholangiocarcinoma and Downregulation of LRRK2 Suppresses Tumor Progress In Vitro

Abstract

Background: The leucine-rich repeat kinase 2 (LRRK2) gene was confirmed to be associated with a variety of diseases, while the physiological function of LRRK2 remains poorly understood. Intrahepatic cholangiocarcinoma (ICC) has over the last 10 years become the focus of increasing concern largely. Despite recent progress in the standard of care and management options for ICC, the prognosis for this devastating cancer remains dismal.

Methods: A total of 57 consecutive ICC patients who underwent curative hepatectomy in our institution were included in our study. We conduct a retrospective study to evaluate the prognostic value of LRRK2 in ICC after resection. The mechanism of LRRK2 in ICC development was also investigated in vitro.

Results: All patients were divided into two groups according to the content of LRRK2 in the tissue microarray blocks via immunohistochemistry: low-LRRK2 group (n = 33) and high-LRRK2 group (n = 24). The recurrence-free survival rate of high-LRRK2 group was significantly poorer than that of low-LRRK2 group (P = 0.010). Multivariate analysis showed high-LRRK2 was the prognostic factor for recurrence-free survival after hepatectomy. We demonstrated that downregulation of LRRK2 depressed the proliferation and metastasis of ICC cells in vitro.

Conclusion: We provide evidence that LRRK2 was an independent prognostic factor for ICC in humans by participating in the proliferation and metastasis of ICC cells.

Keywords: Cell migration; Cell proliferation; Intrahepatic cholangiocarcinoma; Leucine-rich repeat kinase 2; Prognosis.