Frontiers in Immunology (Jan 2022)
Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma
Abstract
BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.
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