Systematic Analysis of the Expression and Prognostic Significance of P4HA1 in Pancreatic Cancer and Construction of a lncRNA-miRNA-P4HA1 Regulatory Axis

Abstract EN

Objectives.

Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a crucial role in modulating extracellular matrix component and promoting tumor progression by changing tumor adhesion, migration, and other biological behaviors in some cancers.

However, its expression pattern, biological function, and underlying mechanism in pancreatic cancer remain largely unclear.

Materials and Methods.

In this study, a set of bioinformatics tools were used to analyze the expression of P4HA1 and its prognostic value in pancreatic cancer.

In addition, the mechanism through which P4HA1 promotes the progression of pancreatic cancer was explored by constructing a competing endogenous RNA (ceRNA) regulatory axis.

Results.

It was found that the mRNA and protein expression of P4HA1 was significantly higher in pancreatic cancer tissues than in normal tissues.

Its high P4HA1 expression correlated with poor clinicopathological features (T stage: P=0.0078; N stage: P=0.0124; TNM stage: P=0.0013; pathological grade: P=0.0108) and poor prognosis [OS: HR=1, 95% CI (1-1.01), P=0.00028; DSS: HR=1, 95% CI (1-1.01), P=0.00049; PFI: HR=1.01, 95% CI (1.01-1.02), P=0.0057; and DFI: HR=1, 95% CI (1-1.01), P=0.0034].

The LINC01503/miR-335-5p/P4HA1 axis might mediate the effects of P4HA1 in promoting the progression on pancreatic cancer.

Conclusions.

Collectively, our findings suggest that high expression of P4HA1 may be used as a promising prognostic biomarker and could be considered for the development of a novel therapeutic strategy for pancreatic cancer in the future.