Immunohistochemical Signature Add Prognostic Value in Patients With Early and Intermediate Hepatocellular Carcinoma Underwent Curative Liver Resection

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide; however, accurate prognostic tools are still lacking. We aimed to identify immunohistochemistry (IHC)-based signature as a prognostic classifier to predict recurrence and survival in patients with HCC at Barcelona Clinic Liver Cancer (BCLC) early- and immediate-stage. In total, 567 patients who underwent curative liver resection at two independent centers were enrolled. The least absolute shrinkage and selection operator regression model was used to identify significant IHC features, and penalized Cox regression was used to further narrow down the features in the training cohort (n = 201). The candidate IHC features were validated in internal (n = 101) and external validation cohorts (n = 265). Three IHC features, hepatocyte paraffin antigen 1, CD34, and Ki-67, were identified as candidate predictors for recurrence-free survival (RFS), and were used to categorize patients into low- and high-risk recurrence groups in the training cohort (P < 0.001). The discriminative performance of the 3-IHC_based classifier was validated using internal and external cohorts (P < 0.001). Furthermore, we developed a 3-IHC_based nomogram integrating the BCLC stage, microvascular invasion, and 3-IHC_based classifier to predict 2- and 5-year RFS in the training cohort; this nomogram exhibited acceptable area under the curve values for the training, internal validation, and external validation cohorts (2-year: 0.817, 0.787, and 0.810; 5-year: 0.726, 0.662, and 0.715; respectively). The newly developed 3-IHC_based classifier can effectively predict recurrence and survival in patients with early- and intermediate-stage HCC after curative liver resection.