Inflammation-Related Biomarker COMMD10 Values Up BCLC Staging in Individualized Prediction of Overall Survival in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) patients diagnosed with the same clinic stage by Barcelona Clinic Liver Cancer (BCLC) system show different prognosis due to coexistence of inflammation and tumor heterogeneity. Here, we aimed to seek for inflammation-related molecular biomarkers for accurately predicting diagnosis and prognosis of HCC. Methods: In this multicenter and retrospective analysis, we included 516 patients with HCC from three Chinese hospitals: Nanfang Hospital (Guangzhou, China), Zhujiang Hospital (Guangzhou, China) and Yuebei Hospital (Shaoguan, China). COMMD10 was screened out from inflammation-induced HCC using real-time PCR analysis. Nomogram based on COMMD10 and BCLC stage was established and validated. The predictive accuracy and discriminative ability of the nomogram was determined by concordance index and calibration curve. The primary endpoint was overall survival (OS). In vitro and in vivo assays were performed to investigate the role of COMMD10 in HCC. The potential molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, immunoprecipitation. Findings: The nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in multicenter cohorts. COMMD10 can stratify early-stage HCC (BCLC stage 0 and A) patients into two risk groups with significantly different OS. Mechanistically, COMMD10 suppressed proliferation in vitro and in vivo by interacting with Rel homology domain of p65 and potentiating apoptosis by modulating Bcl-2/Bax/caspase-9/3 pathway in HCC. Interpretation: COMMD10 is a powerful prognostic biomarker and values up BCLC staging to predict OS for HCC, especially for identifying early-stage HCC patients who could benefit from individual therapy. Funding Statement: This work was supported by the National Natural Science Foundation of China [NO.81672992,81602685]; the Natural Science Foundation of Guangdong Province [NO. 2017A030313486]. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of Nanfang Hospital of Southern Medical University, and all participants provided written informed consent prior to surgery. It also conforms to the provisions of the Declaration of Helsinki.