Clinical significance of citrullinated glial fibrillary acidic protein in predicting outcomes in hepatocellular carcinoma.

BACKGROUND

Citrullination is a post-translational modification mediated by calcium-dependent peptidylarginine deiminases that results in notable changes in protein structure and function. Glial fibrillary acidic protein (GFAP), which is highly vulnerable to peptidylarginine deiminases-mediated modification, has been found to be elevated in activated hepatic stellate cells, with GFAP-positive hepatic stellate cells and myofibroblasts accumulating within and around areas of hepatic fibrosis. Although recent studies have shown that the expression of citrullinated GFAP (cit-GFAP) increases during hepatic fibrosis, its expression pattern and functional roles in hepatocellular carcinoma (HCC) remain unclear.

AIM: To determine whether cit-GFAP expression influences the recurrence and survival of patients undergoing hepatic resection for HCC.

METHODS

We retrospectively analyzed 169 patients with HCC who underwent hepatic resection. Based on the immunohistochemical staining of resected specimens, the enrolled patients were stratified into two groups according to cit-GFAP expression: Low (-/1 +) or high (2 +/3 +) levels of expression. Kaplan-Meier survival curves were constructed to assess overall survival and recurrence-free survival, and comparisons between groups were performed using the log-rank test.

RESULTS

The median follow-up duration was 33 months (range, 1-183). High cit-GFAP expression, identified in 81 patients (48.2%), was significantly associated with male sex, hepatitis B virus positivity, and higher Edmonson-Steiner grade. No associations were found between age, diabetes, hypertension, cirrhosis, Child-Pugh classification, major portal vein invasion, hematological or biochemical parameters, tumor size, or number. Patients exhibiting high cit-GFAP expression demonstrated significantly poorer overall survival. Multivariate Cox analysis identified large tumor size (hazard ratio: 2.967; 95% confidence interval: 1.097-8.024; P = 0.032) and high cit-GFAP expression (hazard ratio: 2.753; 95% confidence interval: 1.015-7.464; P = 0.047) as independent predictors of poor postoperative survival. Although recurrence rates were high in patients with high cit-GFAP expression, the difference was not statistically significant.

CONCLUSION

Following curative resection in patients with HCC, high cit-GFAP expression may serve as a potential prognostic biomarker, although further validation through independent cohort studies is warranted.