To investigate the expression, biological function and clinical relevance of melanoma cell adhesion molecule (MCAM) in hepatocellular carcinoma (HCC), and its role in the survival prognosis and immunotherapy response of HCC patients.

The MCAM mRNA expression level and clinical information were retrieved from TCGA, UCSC Xena and GEO databases. Differential expression analysis was performed using ggplot2. The "survival" and "survminer" R packages were used for survival analysis. The expression of MCAM protein was evaluated by the data base of Clinical Proteomic Tumor Analysis Consortium (CPTAC). Gene ontology (GO) functional and KEGG pathway enrichment analyses were conducted by LinkedOmics. Single-sample gene set enrichment analysis (ssGSEA) and TIMER database were used to evaluate the relationship between immune cell infiltration and immune checkpoints. Immunohistochemical assay was validated by using clinical samples. The response to immunotherapy was predicted by the BEST database.

Multiomics analysis based on the TCGA-LIHC data set, GEO, UALCA and CPTACP databases showed that MCAM was highly expressed in HCC tissues. In TCGA-LIHC data set, the overall survival (OS) and progression-free survival (PFS) of patients with high expression of MCAM were significantly lower than those with low MCAM expression (HR=0.70, 0.68; both P<0.05). In GSE144269 and GSE54236 databases, the OS of patients with high expression of MCAM was lower than that of patients with low MCAM expression (HR=0.67, 0.72; both P<0.05). UALCA database demonstrated that high expression of MCAM in HCC patients was positively correlated with clinical stage, tumor grade and lymph node metastasis (all P<0.05). In TCGA-LIHC data set, the area under the ROC curve (AUC) of MCAM expression was 0.921 (95%CI: 0.887-0.954), indicating that MCAM had high diagnostic efficiency. GO functional and KEGG pathway enrichment analyses showed that the co-expressed genes of MCAM participated in the immune response pathway, including Th1/Th2 cell differentiation. High MCAM expression significantly affected the level of immune cell infiltration and participated in multiple cancer-promoting signal pathways. Immunohistochemistry found high expression of MCAM protein in HCC tissues. BEST analysis demonstrated that high MCAM expression might predict better response to targeted therapy of PD-1, PD-L1 and CTLA-4.

MCAM is highly expressed in HCC, which is associated with poor prognosis and immune regulation of HCC patients. MCAM can be used as a valuable biomarker for cancer prognosis and a potential predictor for clinical efficacy of immunotherapy.