Abstract
Objective: Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), a key enzyme in collagen synthesis, comprises two identical alpha subunits and two beta subunits. However, the immunomodulatory role of P4HA1 in tumor immune microenvironment (TIME) remains unclear. This study aimed to evaluate the prognostic value of P4HA1 in pan-cancer and explore the relationship between P4HA1 expression and TIME. Methods: P4HA1 expression, clinical features, mutations, DNA methylation, copy number alteration, and prognostic value in pan-cancer were investigated using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data. Pathway enrichment analysis of P4HA1 was performed using R package “clusterProfiler.” The correlation between immune cell infiltration level and P4HA1 expression was analyzed using three sources of immune cell infiltration data, including ImmuCellAI database, TIMER2 database, and a published work. Results: P4HA1 was substantially overexpressed in most cancer types. P4HA1 overexpression was associated with poor survival in patients. Additionally, we discovered that P4HA1 expression was positively associated with infiltration levels of immunosuppressive cells, such as tumor-associated macrophages, cancer-associated fibroblasts, nTregs, and iTregs, and negatively correlated with CD8+ T and NK cells in pan-cancer. Conclusions: Our results highlighted that P4HA1 might serve as a potential prognostic biomarker in pan-cancer. P4HA1 overexpression is indicative of an immunosuppressive microenvironment. P4HA1 may be a potential target of immunotherapy.
Highlights
Cancer is the main cause of human death (Siegel et al, 2020)
We first assessed the expression of P4HA1 using the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cell Line Encyclopedia (CCLE) data
We found that P4HA1 was overexpressed in 26 of 33 cancers types, including ACC, BLCA, BRCA, CHOL, COAD, DLBC, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, OV, PAAD, PRAD, READ, SKCM, STAD, TGCT, THCA, THYM, UCEC, and UCS
Summary
Huge progress has been made in cancer-related treatment technologies in recent years, patient prognosis remains very low, mainly because most patients are diagnosed in the final stage and lack effective specific therapeutic targets. Onco-immunotherapies, such as immune checkpoint blockade inhibitors, have revolutionized the prognosis of cancer patients, but most patients remain insensitive to immunotherapy It is urgent to investigate the underlying mechanism of tumors and determine novel key biomarkers and potential immunotherapy targets for tumor patients. Recent studies have demonstrated that immunosuppressive tumor immune microenvironment (TIME) is critical in developing tumor progression and weakening the response of tumor patients to immunotherapy (Taki et al, 2021; Wang et al, 2021). Immune cells in TIME were remodeled and lost their original function. The number of biomarker genes which can predict the status of TIME is small
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