Expression and prognostic significance of MLH1 and GPRC5C in resectable hepatocellular carcinoma

It has recently been shown that mut-L homolog 1 (MLH1), frequently lost in cancer initiation and progression, inhibited pancreatic cancer metastatic potential by downregulating G-protein coupled receptor C5C (GPRC5C). However, their expression and prognostic significance in hepatocellular carcinoma (HCC) has not been elucidated, especially for GPRC5C.

We detected MLH1 and GPRC5C expression using the tissue microarray-based immunohistochemical staining in tumor and matched adjacent non-tumor liver (ANL) specimens from 230 patients who underwent radical resection for HCC. The correlations between staining H-scores and clinicopathologic parameters, overall and disease-free survival were then evaluated. Finally, the prognostic value of the genes was evaluated in the online publicly available Kaplan-Meier Plotter database.

Firstly, MLH1 expression was much lower in HCC than in ANL tissues, while GPRC5C had the opposite change. Spearman's correlation coefficient analysis showed that MLH1 and GPRC5C were of a strong negative correlation (P < 0.001). In addition, MLH1 was negatively related to AFP level, and GPRC5C was positively linked to tumor size and vascular invasion. Univariately, high MLH1 or GPRC5C expression was remarkably associated with better or poorer overall and disease-free survival, respectively. In multivariate analyses, GPRC5C remains to be a powerful determinant for both overall and disease-free survival, while MLH1 was significant only for overall survival. Lastly, MLH1 predicted recurrence-free and progression-free survival in the Kaplan-Meier Plotter, GPRC5C might have the adverse effect, although being not statistically significant.

MLH1 and GPRC5C have divergent expressions with an inverse correlation and function as promising novel prognostic indicators in resectable HCC.