LAPTM4B-35 overexpression is a risk factor for tumor recurrence and poor prognosis in hepatocellular carcinoma

• Published in: Journal of cancer research and clinical oncology 2010-02, Vol.136 (2), p.275-281
• Main Authors: Yang, Hua, Xiong, Fu Xia, Lin, Ming, Yang, Yu, Nie, Xiu, Zhou, Rou Li
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Cancer Research; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - secondary; Carcinoma, Hepatocellular - surgery; Disease-Free Survival; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Glycoproteins; Hematology; Hepatectomy; Humans; Immunohistochemistry; Internal Medicine; Liver; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Membrane Proteins - metabolism; Middle Aged; Neoplasm Recurrence, Local - metabolism; Neoplasm Staging; Oncogene Proteins - metabolism; Oncology; Original Paper; Pharmacology. Drug treatments; Predictive Value of Tests; Prognosis; Risk Factors; Survival Analysis; Tumors; Up-Regulation
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-009-0659-4

Purpose Lysosomal protein transmembrane 4 beta-35 (LAPTM4B-35) is a tetra-transmembrane glycoprotein that is abundantly localized on membrane-bound organelles including endosomes and lysosomes, and promotes cell proliferation and tumorigenesis through regulation of cell cycle and signaling pathways. The aim of the present study is to determine the potential clinical implications of LAPTM4B-35 expression in hepatocellular carcinoma (HCC). Methods Immunohistochemistry assay was used to determine the expression of LAPTM4B-35 protein in normal and HCC tissues from 71 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters, including gender, age, background liver, viral status, tumor size, portal vein invasion, histopathological differentiation, serum AFP level, TNM staging and recurrence of HCC were assessed by Chi-squared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression (Proportional hazard model) was adopted for multivariate analysis of prognostic factors. Results LAPTM4B-35 immunoreactivity was negative or low in normal liver tissues, but high in HCC tissues (51/71, 71.8%). The overexpression of LAPTM4B-35 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with patients with the low expression of LAPTM4B-35. On multivariate analysis, LAPTM4B-35 expression was found to be an independent prognostic factor for OS and DFS (P = 0.018 and P = 0.001, respectively). Conclusion LAPTM4B-35 expression showed a strong association with the potencies of recurrence and metastasis and progression of HCC, and that may be applied as a novel marker for the prediction of recurrence and metastasis potency of HCC, and helpful for improving the diagnosis, prognosis and treatment of HCC.