Combined lysosomal protein transmembrane 4 beta-35 and argininosuccinate synthetase expression predicts clinical outcome in hepatocellular carcinoma patients.

PURPOSE

The newly-identified lysosomal protein transmembrane 4 beta-35 (LAPTM4B-35) plays important roles in tumor progression and metastasis, while argininosuccinate synthetase (ASS) provides arginine as an indispensable nutrient for hepatocellular carcinoma (HCC). The present study investigated the clinical significance of the coexpression of LAPTM4B-35 and ASS in HCC patients on determining the prognosis.

METHODS

Immunohistochemistry was used to evaluate the expression of LAPTM4B-35 and ASS in HCC tissues and paired noncancerous liver samples from 71 patients. The correlation of combined LAPTM4B-35 and ASS expression with selected clinicopathologic parameters was assessed with the chi-squared test. Patient survival and differences in survival were determined by the Kaplan-Meier method and the log-rank test. A Cox regression analysis was adopted for a multivariate analysis of the prognostic factors.

RESULTS

Combined LAPTM4B-35 and ASS expression was significantly associated with TNM stage and portal vein invasion. In addition, patients with HCCs expressing both LAPTM4B-35 and ASS exhibited both markedly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001). According to the multivariate analyses, combined LAPTM4B-35 and ASS expression was found to be an independent prognostic factor for OS and DFS (P = 0.039 and P = 0.035, respectively).

CONCLUSION

The overexpression of LAPTM4B-35 in combination with positive ASS expression is a negative prognostic marker for HCC.