Unraveling the Complexity: Expression Patterns and Prognostic Value of Cell Adhesion Junction Regulatory Genes in Hepatocellular Carcinoma

Abstract

Abstract This study investigates the impact of cell adhesion junction-related genes on the prognosis of primary hepatocellular carcinoma (HCC) while exploring potential correlations between adhesion junction mechanisms and the tumor immune microenvironment. A total of 60 cell adhesion junction-related genes were carefully analyzed to construct a risk signature. Through differential expression, univariate Cox, and LASSO analyses, combined with patient data from the TCGA database, the risk signature's validity was rigorously confirmed using survival analysis and independence testing. Further exploration involved analyzing the model's correlation with the tumor immune microenvironment and its responsiveness to common therapeutic drugs. The study identified ten adherens junction-related genes integral to the risk signature, with FYN and PTPRB acting as protective effectors of HR < l, and PARD3, SSX2IP, RAC3, CDC42, NECTIN1, WASF1, RAC1, and SMAD2 serving as risk effectors of HR > l. Notably, the low-risk group exhibited significantly improved prognosis (p < 0.0001), with respective area under the curve (AUC) values at 1, 3, and 5 years of 0.799, 0.708, and 0.645. Furthermore, the low-risk subgroup displayed heightened immune cell activity, whereas the high-risk group demonstrated elevated expression of specific immune checkpoints, indicating a potential benefit from immunotherapy. The G2M checkpoint, PI3k-AKT-mTOR signaling pathway, DNA damage repair, and MTORC1 signaling pathway were positively associated with the risk score, offering crucial insights into the underlying mechanisms at play.