P4HA1, a Prognostic Biomarker that Correlates With Immune Infiltrates in Lung Adenocarcinoma and Pan-Cancer

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.

P4HA1, transcriptionally activated by STAT1, promotes esophageal cancer progression

“…Functional experiments subsequently revealed that P4HA1 knockdown remarkably repressed EC cell viability and proliferation (Figure 2e–g) and promoted the apoptosis (Figure 2h). P4HA1, as a key enzyme in collagen synthesis, contributes to cancer progression by promoting collagen synthesis 6 . Collagen is a major component of the tumor microenvironment, which contributes to cancer development 14 .…”

“…P4HA1, as a key enzyme in collagen synthesis, contributes to cancer progression by promoting collagen synthesis. 6 Collagen is a major component of the tumor microenvironment, which contributes to cancer development. 14 In the current study, the result from western blot displayed that the protein levels of collagens (COL1A1 and COL4A1) in EC cells were markedly reduced by P4HA1 knockdown (Figure 2i).…”

“…Prolyl 4‐hydroxylase alpha polypeptide I (P4HA1) accelerates cancer fibrosis by promoting collagen synthesis, which facilitates metastasis 6 . P4HA1 is reported to be significantly upregulated in various human malignant tumors, including lung adenocarcinoma, colorectal cancer and breast cancer, and it can be used as a prognostic biomarker in cancers 6–8 .…”

“…Prolyl 4-hydroxylase alpha polypeptide I (P4HA1) accelerates cancer fibrosis by promoting collagen synthesis, which facilitates metastasis. 6 P4HA1 is reported to be significantly upregulated in various human malignant tumors, including lung adenocarcinoma, colorectal cancer and breast cancer, and it can be used as a prognostic biomarker in cancers. [6][7][8] Although it's widely suggested that P4HA1 is a risk factor affecting the progression of multiple cancers, nevertheless, the function of P4HA1 in EC is still unclear, which deserves further research.…”

A novel prognostic biomarker CD3G that correlates with the tumor microenvironment in cervical cancer

“…Additionally, understanding the infiltration of immune cells will greatly help to guide clinical treatment of tumors ( 9 ). Recently, research on the TME has shown that the immune infiltration analysis and ImmuneScore could be jointly used to improve the prediction of cancer prognosis ( 10 , 11 ). For example, the TME-related ImmuneScore in colorectal cancer is an effective indicator of metastasis and prognosis ( 11 ).…”