ORIGINAL RESEARCH article

Front. Genet.

Sec. Cancer Genetics and Oncogenomics

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1487046

This article is part of the Research TopicEmerging Relevance of Molecular Profiling in Global Cancer Research and ManagementView all 5 articles

Metabolic Reprogramming and Prognostic Modeling in Pancreatic Cancer: Insights from WGCNA

Provisionally accepted
  • 1Air Force General Hospital PLA, Beijing, China
  • 2Peking University Shougang Hospital, Beijing, China

The final, formatted version of the article will be published soon.

Purpose: Metabolic reprogramming plays a crucial role in multiple malignant features of pancreatic cancer (PC). However, few studies have comprehensively examined metabolic features of PC and provided guidance for their treatment.Methods: This study tried to identify metabolism-associated hub genes based on metabolic phenotypic levels through weighted gene co-expression network analysis, and constructed a risk model for PC, then verified its accuracy and explored the potential mechanisms.Results: We screened out five metabolic hub and prognostic genes (DLX3, HMGA2, SPRR1B, MYEOV, and FAM111B) and constructed a novel metabolism-associated gene signature to predict the prognosis of PC. The model was verified efficacy and demonstrated with good performance through analysis of Kaplan-Meier plotter, receiver operating characteristic curves, comparing with reported models, application in predicting drug sensitivity and constructing a nomogram model. Correlation analysis revealed a close association between the levels of risk score and DNA damage response (DDR, correlation coefficient: 0.41, P < 0.001). Enrichment analysis indicated that risk scores were derived from multiple metabolic or proliferative pathways, providing further evidence that metabolism may mediate DDR to affect PC survival.Conclusion: Through bioinformatics analysis, we identified five prognostic relevant differentially expressed genes highlighting the role of metabolism-associated factors in pancreatic cancer, which reveals a strong correlation ship with DDR, offering new insights into treatment strategies that combine metabolism with DDR.

Keywords: Pancreatic Cancer, predictable model, Metabolism, DNA damage repair, bioinformatics

Received: 28 Aug 2024; Accepted: 29 May 2025.

Copyright: © 2025 Song, Sun, Di, Liu, Kang, Ren and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Zhuo Song, Air Force General Hospital PLA, Beijing, China
Gang Ren, Peking University Shougang Hospital, Beijing, China
Yingjie Wang, Air Force General Hospital PLA, Beijing, China

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