Novel insights into the progression and prognosis of the calpain family members in hepatocellular carcinoma: a comprehensive integrated analysis

Objectives: The goal of our bioinformatics study was to comprehensively analyze the association between the whole calpain family members and the progression and prognosis of hepatocellular carcinoma (HCC).Methods: The data were collected from The Cancer Genome Atlas (TCGA). The landscape of the gene expression, copy number variation (CNV), mutation, and DNA methylation of calpain members were analyzed. Clustering analysis was performed to stratify the calpain-related groups. The least absolute shrinkage and selection operator (LASSO)-based Cox model was used to select hub survival genes.Results: We found 14 out of 16 calpain members expressed differently between tumor and normal tissues of HCC. The clustering analyses revealed high- and low-risk calpain groups which had prognostic difference. We found the high-risk calpain group had higher B cell infiltration and higher expression of immune checkpoint genes HAVCR2, PDCD1, and TIGHT. The CMap analysis found that the histone deacetylase (HDAC) inhibitor trichostatin A and the PI3K-AKT-mTOR pathway inhibitors LY-294002 and wortmannin might have a therapeutic effect on the high-risk calpain group. The DEGs between calpain groups were identified. Subsequent univariate Cox analysis of each DEG and LASSO-based Cox model obtained a calpain-related prognostic signature. The risk score model of this signature showed good ability to predict the overall survival of HCC patients in TCGA datasets and external validation datasets from the Gene Expression Omnibus database and the International Cancer Genome Consortium database.Conclusion: We found that calpain family members were associated with the progression, prognosis, and drug response of HCC. Our results require further studies to confirm.