Abstract
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.
Highlights
Pancreatic cancer is one of the most malignant tumors with the worst prognosis in the world, and it ranks seventh among the cancer-related deaths in the world and fourth amid all the cancer-related mortalities in the United States; annually, about 432,000 patients die of pancreatic cancer every year[1]
Prolyl 4-hydroxylase subunit α1 (P4HA1) was markedly overexpressed in most tumors, especially in kidney and pancreatic cancers (Figure 1(a))
Afterwards, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze the expression of P4HA1 in pan-cancer, in order to further quantitatively verify its expression in various tumors
Summary
Pancreatic cancer is one of the most malignant tumors with the worst prognosis in the world, and it ranks seventh among the cancer-related deaths in the world and fourth amid all the cancer-related mortalities in the United States; annually, about 432,000 patients die of pancreatic cancer every year[1]. Some progress has been made in the field of combined and precision therapy for pancreatic cancer. Overall prognosis remains very poor with a 5-year survival rate of less than 6%2. This makes the cancer one of the deadliest malignant tumors worldwide. P4HA1 is responsible for newly synthesized collagen chains and plays a significant role in the formation and stability of the triple helix region of newly synthesized collagen chains. It is the key catalytic subunit in regulating collagen biosynthesis[3]. Recent studies found that P4HA1 could regulate extracellular collagen synthesis and secretion and were closely related to the progression of some tumors, such as breast cancer[4], prostate cancer[5], and glioma[6, 7] by changing tumor adhesion, migration, and other biological
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