Yanqin Chen, Moazzam Ali, Muhammad Bilal Tayyab, Muhammad Majid Nazir, Muhammad Umar, Salman Khan, Danyah Mohamed Ismail, Mostafa A Abdel-Maksoud, Hossam Ebaid, Abdulaziz Alamri, Saeedah Almutairi, Taghreed N Almanaa, Bushra Hafeez Kiani
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引用次数: 0
Abstract
Background: Cancer is a multifaceted disease characterized by unregulated cell proliferation, evasion of apoptosis, and metastasis. Recent studies have highlighted the importance of extracellular matrix remodeling and post-translational modifications in tumorigenesis. Prolyl 3-hydroxylase 1 (P3H1), an enzyme involved in collagen hydroxylation, has gained attention for its role in cancer progression.
Methods: This study investigates P3H1 expression, prognostic value, and functional relevance across multiple human cancers using a combination of bioinformatic and experimental approaches.
Results: Using The Cancer Genome Atlas (TCGA) data from TIMER2.0 and UALCAN databases, we observed a significant upregulation of P3H1 mRNA and protein in various cancers. Prognostic analysis using GEPIA2 and KM plotter revealed that high P3H1 expression correlates with poorer overall survival in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and liver hepatocellular carcinoma (LIHC). Further, genetic and promoter methylation analyses showed low mutation frequencies and reduced methylation of P3H1 in specific cancer types. Functional and pathway enrichment analyses indicated that P3H1 is involved in collagen formation, endoplasmic reticulum activity, and pathways such as ECM-receptor interaction and PI3K-Akt signaling. Validation by enzyme linked immunosorbent assay in COAD patient serum samples demonstrated significantly elevated P3H1 levels compared to healthy controls, with an AUC approaching 1.0 by receiver operating characteristic (ROC) curve analysis. This suggests its potential as a diagnostic biomarker. Additionally, functional experiments were conducted in COAD cells to assess P3H1's role in tumorigenesis. Knockdown of P3H1 in HCT116 cells resulted in a significant reduction in cell proliferation, colony formation, and migratory abilities of these cells.
Conclusion: These findings emphasize P3H1's relevance in COAD, KIRC, and LIHC pathogenesis and possible utility in clinical diagnosis.
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