Downregulated expression of CFHL1 is associated with unfavorable prognosis in postoperative patients with hepatocellular carcinoma.

Abstract

Complement factor H-related protein 1 (CFHL1) was recently reported to be a potential biomarker in several types of cancer. CFHL1, however, has not been found to be of prognostic value in hepatocellular carcinoma (HCC) to date. In the present study, the expression levels of CFHL1 were evaluated in 8 pairs fresh frozen tissue samples using western blotting. Furthermore, the expression level of CFHL1 was evaluated in 76 pairs of formalin-fixed, paraffin-embedded (FFPE) HCC and peritumoral tissues (expression pattern cohort), and 278 FFPE HCC tissues (prognostic cohort) using tissue microarray-based immunohistochemistry. The Kaplan-Meier method, Cox regression proportional hazard model and receiver operating characteristic curve analysis were used to evaluate prognostic factors. The expression level of CFHL1 was reduced in HCC tissues in 67.1% (51/76) of the cases compared with the corresponding peritumoral tissues. Survival analyses indicated that patients with HCC with low CFHL1 expression had a worse time-to-recurrence (TTR) and overall survival (OS) compared with those with high CFHL1 expression in the prognostic cohort (P=0.002 for OS and P=0.017 for TTR). Both univariate and multivariate analyses indicated that CHFL1 was an independent prognostic factor for TTR and OS (P=0.017 and P=0.002, respectively). In addition, The Cancer Genome Atlas (TCGA) and Human Protein Atlas were used for further validation. Furthermore, a prognostic model included tumor size, tumor number, liver cirrhosis and CFHL1 expression was evaluated. The results of the present study demonstrated that CFHL1 was downregulated in HCC and its level was associated with patient prognosis; therefore, CFHL1 is a potential prognostic marker for HCC.