The expression of chitinase 3-like 1: A novel prognostic predictor for hepatocellular carcinoma

摘要

Objectives: Chitinase 3-like 1 (CHI3L1) is associated with poor prognosis of various human cancers. However, the clinical and prognostic significance of CHI3L1 in hepatocellular carcinoma (HCC) is largely unknown. The aim of the present study is to investigate the expression of CHI3L1 in human HCC cell lines, clinical HCC specimens and its association with expressions of phosphorylated-Akt (p-Akt), E-cadherin and prognostic significance. Methods: The protein level of CHI3L1 in HCC cell lines was evaluated by western blot. The mRNA and protein levels of CHI3L1 in 19 self-paired HCC specimens were assessed by RT-PCR and western blot assays. The clinical and prognostic significance of CHI3L1 in 70 cases of HCC patients was determined by immunohistochemistry. In addition, expressions of p-Akt and E-cadherin were also assessed. Results: The protein level of CHI3L1 paralleled with increased malignant potential of HCC cell lines (P < 0.05). The mRNA and protein levels of CHI3L1 in HCC tissues were up-regulated compared with those in adjacent peritumoral tissues and further increased in tumors with metastasis (P < 0.05). Clinicopathological analysis showed that positive CHI3L1 expression was significantly associated with larger tumor size, capsular invasion, advanced TNM stages and status of metastasis (P = 0.035, 0.003, 0.023 and 0.003, respectively). Furthermore, CHI3L1 expression was positively correlated with high level of p-Akt (r = 0.293, P = 0.014), but inversely correlated with expression of E-cadherin (r = -0.267, P = 0.026). Additionally, Kaplan-Meier survival analysis showed that HCC patients with positive CHI3L1 expression had a worse overall survival and disease-free survival compared with those with negative CHI3L1 expression (P < 0.001, respectively). Multivariate analysis identified CHI3L1 as an independent prognostic predictor for overall survival and disease-free survival of HCC patients (P = 0.044 and 0.031, respectively). Conclusions: CHI3L1 plays an essential role in HCC malignancies and may be served as a valuable prognostic biomarker for HCC patients.