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Comprehensive analysis and experiment validation of five cuproptosis-related genes in prognosis, immune infiltration and metabolic characterization of pancreatic cancer

  • 0Department of Gastroenterology, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, China.
Plos One +

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May 14, 2025

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May 14, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Five cuproptosis-related genes (CRGs) were identified as key predictors for pancreatic cancer survival. A novel prognostic model using these genes accurately predicts patient outcomes and may guide precise anti-cancer treatments.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Cuproptosis, a novel cell death pathway, has an unclear role in pancreatic cancer (PC) prognosis.
  • Identifying key genes associated with cuptosis is crucial for understanding PC progression.

Purpose Of The Study

  • To identify cuptosis-related genes (CRGs) associated with pancreatic cancer prognosis.
  • To construct and validate a prognostic model based on CRGs.
  • To investigate the underlying mechanisms and functional roles of these CRGs in PC.

Main Methods

  • Utilized TCGA and GTEx databases to identify differentially expressed CRGs (DECRGs).
  • Employed Cox regression and LASSO analyses to screen for hub genes.
  • Validated gene expression and protein levels using RT-qPCR and Western blotting.
  • Assessed the functional role of LIPT1 in PC cell lines via CCK8, colony formation, and Transwell assays.

Main Results

  • Five hub genes (PDP1, DLAT, DBT, LIAS, LIPT1) were identified as significantly associated with overall survival (OS) in pancreatic cancer.
  • A prognostic model based on these five CRGs demonstrated that a low-risk score correlates with longer OS.
  • High-risk scores were associated with advanced clinicopathological features, and age, N stage, and RiskScore were independent risk indicators.
  • LIPT1 knockdown inhibited proliferation and invasion in pancreatic cancer cell lines, suggesting its oncogenic role.

Conclusions

  • A novel five-CRG prognostic model for pancreatic cancer was developed, offering accurate survival prediction.
  • The identified CRGs, particularly LIPT1, play significant roles in pancreatic cancer progression.
  • This model and findings provide valuable insights for developing precise anti-cancer therapeutic strategies for pancreatic cancer.