[PLXNA1 is highly expressed in hepatocellular carcinoma and affects patients' survival and immune microenvironment].

ABSTRACT

OBJECTIVE: To investigate PLXNA1 expression in hepatocellular carcinoma (HCC) and explore its biological function and impacts on patients' survival outcomes and immune microenvironment. METHODS: Bioinformatic analysis of highly expressed immune-related genes in HCC were performed using TCGA database and Immport website, and 7 genes associated with the survival outcomes of the patients were identified using univariate Cox regression analysis, Gene Expression Profiling Interactive Analysis, and Kaplan Meier plotter website. The expression profile of PLXNA1 in HCC was verified using GEO database. The impact of PLXNA1 expression on survival outcomes of HCC patients was analyzed using TCGA database, Kaplan Meier, and timeROC curve analyses, and its association with immune cell infiltration was explored using TIMER website, CIBERSORT, and ssGSEA. Immunohistochemmistry was used to detect PLXNA1 expression in clinical specimens of HCC and adjacent tissues, and the correlation of PLXNA1 expression level with the patients' survival was analyzed. RT-qPCR was used to examine PLXNA1 expressions in different HCC cell lines, and the effects of PLXNA1 knockdown on proliferation and migration of SMMC-7721 cells were evaluated using CCK-8 and Transwell assays. RESULTS: Bioinformatic analyses suggested that PLXNA1 was highly expressed in HCC, and its high expression was associated with poor survival outcomes of the patients. PLXNA1 expression level was significantly correlated with immune cell infiltration in HCC. Immunohistochemmistry showed that compared with the adjacent tissues, HCC tissues had significantly higher PLXNA1 expressions, which were associated with a poor patient survival and served also as a diagnostic indicator for HCC (AUC= 0.9346). In cultured HCC cell lines, SMMC-7721 cells showed a higher PLXNA1 expression than HL-7702 cells, and PLXNA1 knockdown significantly suppressed proliferation and migration of SMMC-7721 cells. CONCLUSION: PLXNA1 is highly expressed in HCC to promote tumor cell migration and proliferation and affect the patients' survival outcomes and immune microenvironment.