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

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.

Multi-omics analysis reveals cuproptosis and mitochondria-based signature for assessing prognosis and immune landscape in osteosarcoma

“…P4HA1 has been found to exert a carcinogenic effect. In esophageal cancer, activation of P4HA1 by STAT1 transcription could boost cell growth and survival (28,29). Zhou et al demonstrated that elevated expression of P4HA1 indicates dismal prognosis in cases with head and neck cancer (HNC).…”

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

“…По данным Chen T. и соавт., экспрессия miR-335-5p в плазме крови была снижена у пациентов с трижды негативным раком молочной железы по сравнению со здоровым контролем [50], в то время как повышенная экспрессия miR-335-5p приводила к ингибированию ускользания от иммунного ответа, а полное отсутствие miR-335-5p способствовало росту опухоли. В работах на клетках рака поджелудочной железы [51], адренокортикального рака [52] и колоректального рака [53] пониженная экспрессия miR-335-5p была ассоциирована с более неблагоприятным прогнозом заболевания. И наоборот, повышение экспрессии miR-335-5p в основном приводило к снижению пролиферации и миграции опухолевых клеток [53][54][55].…”

The Role of microRNA in Pancreatic Cancer

“…Gene set variability analysis (GSVA) was used to determine and validate the prognostic signature of the miRNA-based path for PC (miPPSPC) and the prognostic signature of the PC mRNA (mPPSPC) path in independent data sets [91]. MiPPSPPC has been optimized by combining clinical parameters.…”

“…For example, circulating miR- 155, 181a, 181b, 196a, 200a, 200b, and 212 were reported as significantly elevated in patients with chronic pancreatitis compared to healthy controls [75,80,110]. Li et al showed that serum levels of miR-200a and miR-200b are similar in patients with pancreatic cancer and pancreatitis, although they are elevated compared to healthy controls [91]. Interestingly, the miR-200 family can inhibit the transition from the epithelium to mesenchymes and therefore may play a direct signaling role [98].…”