BIRC5 and PRLR Might Be Novel Immune-Related Prognostic Biomarkers in Adrenocortical Carcinoma (ACC)

Abstract Background: Adrenocortical carcinoma (ACC) is a highly aggressive tumor，which occurs in adrenal cortex. This study aims to identify new immune-related molecular biological markers and therapeutic targets in ACC patients. Results: First, we identified 134 genes by constructing weighted gene co-expression network. Among them, two genes (BIRC5 and PRLR) were eventually regarded as immune-related prognosis biomarkers on the basis of The Immunology Database and Analysis Portal (ImmPort) database. The validation of mRNA level was meaningful (based on Oncomine database and TCGA-ACC). Four methods (overall survival (OS) analysis, disease-free survival (DFS) analysis, stage plot and expression value comparison) were used in GEPIA to verify that PRLR and BIRC5 have significant correlation with the prognosis of ACC. Several other methods including survival analysis, analysis of variance, the spearman correlation analysis, distance correlation analysis and receiver operating characteristic curve were also used for the external validation of them in GEO datasets (GSE10279, GSE19750, GSE76019 and GSE76021). Furthermore, we evaluated the relationship between hub gene expression of and the degree of immune cell infiltration in ACC by ESTIMATE algorithm and ssGSEA. BIRC5 expression was significantly positively related to activated CD4 T cell and type 2 T helper cell. And PRLR expression was positively related to CD56dim NK cell and type 17 T helper cell. Moreover, Gene set enrichment analysis (GSEA) suggested that PRLR has strong correlation with neuroactive ligand receptor interaction and BIRC5 was significantly enriched in cell cycle. In addition, according to Drug Signatures Database (DSigDB), BIRC5 were significantly enriched in “resveratrol_mcf7_down”, “lucanthone_ctd_00006227”, “8-azaguanine_pc3_down”, “thioguanosine _mcf7_down”, “dasatinib_ctd_00004330”, “monobenzone_pc3_down”. Conclusions: In summary, BIRC5 and PRLR were shown to be related to the prognosis of patients with ACC, indicating them as novel immune-related prognostic biomarkers and immunotherapy targets in ACC.