Intratumoral Fibrosis is a Potential Biomarker in Patients with Hepatocellular Carcinoma Undergoing Liver Resection.

Abstract

Background: Intratumoral fibrosis (ITF) has been demonstrated to influence the prognosis of various fibrotic solid tumors. Thus, this study aimed to validate its role as a potential prognostic biomarker in patients with hepatocellular carcinoma (HCC) undergoing liver resection.

Methods: This investigation enrolled 367 adult patients diagnosed with HCC who underwent liver resection. The patients were classified into high- (score ≥ 2) and low-ITF (score < 2) groups based on a semiquantitative Sirius red staining scale (0-3). IHC staining for CD34 was performed on resected samples to determine microvascular density (MVD) and to investigate the association between ITF and tumor vascularization. Cox proportional hazards regression with backward stepwise selection was employed to identify independent predictors for early HCC recurrence. Moreover, to mitigate the impact of confounding factors, propensity score matching (PSM) was conducted between patients in the high- and low-ITF groups. Lastly, the Kaplan-Meier method was utilized to assess and compare the disease-free survival (DFS) and overall survival (OS) between the two cohorts.

Results: The study categorized patients into high-ITF and low-ITF groups. Backward stepwise Cox regression analysis revealed that liver cirrhosis (P<0.001), serum monocyte count (P<0.001), AFP >200 ng/mL (P<0.001), substantial intratumoral necrosis (P<0.001), presence of intratumoral artery (P<0.001), nodule-in-nodule architecture (P<0.001), and high-ITF (P<0.001) were significantly associated with early HCC recurrence. Furthermore, the results suggested that DFS and OS were significantly shorter in the high-ITF group compared to the low-ITF group, both before and after PSM (P<0.05). Finally, compared to low-ITF HCCs, high-ITF HCCs were more frequently associated with high MVD counts (54.0, IQR: 43.0-67.5 vs. 45.0, IQR: 30.0-58.0, P<0.001).

Conclusion: ITF holds promise as a prognostic biomarker for early recurrence and prognosis in patients with HCC who underwent liver resection, with practical applicability for developing personalized treatment strategies for HCC.