Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Costimulatory molecules have been proven to be the foundation of immunotherapy. However, the potential roles of costimulatory molecule genes (CMGs) in HCC remain unclear. Our study is aimed to develop a costimulatory molecule-related gene signature that could evaluate the prognosis of HCC patients.MethodsBased on The Cancer Gene Atlas (TCGA) database, univariate Cox regression analysis was applied in CMGs to identify prognosis-related CMGs. Consensus clustering analysis was performed to stratify HCC patients into different subtypes and compared them in OS. Subsequently, the LASSO Cox regression analysis was performed to construct the CMGs-related prognostic signature and Kaplan–Meier survival curves as well as ROC curve were used to validate the predictive capability. Then we explored the correlations of the risk signature with tumor-infiltrating immune cells, tumor mutation burden (TMB) and response to immunotherapy. The expression levels of prognosis-related CMGs were validated based on qRT-PCR and Human Protein Atlas (HPA) databases.ResultsAll HCC patients were classified into two clusters based on 11 CMGs with prognosis values and cluster 2 correlated with a poorer prognosis. Next, a prognostic signature of six CMGs was constructed, which was an independent risk factor for HCC patients. Patients with low-risk score were associated with better prognosis. The correlation analysis showed that the risk signature could predict the infiltration of immune cells and immune status of the immune microenvironment in HCC. The qRT-PCR and immunohistochemical results indicated six CMGs with differential expression in HCC tissues and normal tissues.ConclusionIn conclusion, our CMGs-related risk signature could be used as a prediction tool in survival assessment and immunotherapy for HCC patients.
Highlights
Primary liver cancer is an aggressive malignant tumor with high mortality worldwide [1]
The 59 costimulatory molecule-related genes expression levels were compared between Hepatocellular carcinoma (HCC) tumor and normal tissues, we identified 40 differentially expressed genes (DEGs) (P < 0.05)
The area under the curve (AUC) of risk score and tumor stage were 0.739 and 0.671 in 1-year, 0.698 and 0.680 in 3-year, 0.638 and 0.663 in 5-year, respectively (Fig. 7C). These findings suggested that the risk signature might be reliable to predict the overall survival (OS) for HCC patients
Summary
Primary liver cancer is an aggressive malignant tumor with high mortality worldwide [1]. Hepatocellular carcinoma (HCC) is the most common histological subtype and the fourth leading cause of cancer-related mortality, accounts for approximately 90% of all primary liver cancer. Hu et al Cancer Cell International (2022) 22:97 the traditional treatment methods for HCC are systemic chemotherapy, local ablation, TACE (Transhepatic Arterial Chem Otherapy and Embolization) and surgical resection [2]. Some clinical trials related immunotherapy showed different outcomes in improving the prognosis of HCC patients [6,7,8]. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Our study is aimed to develop a costimulatory molecule-related gene signature that could evaluate the prognosis of HCC patients
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