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Hypoxia and lipid metabolism related genes drive proliferation migration and immune infiltration mechanisms in colorectal cancer subtyping

  • 0Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
Scientific Reports +

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January 18, 2025

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January 18, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study reveals that hypoxia- and lipid metabolism-related genes (HLPG) significantly impact colorectal cancer (CRC) prognosis. A new risk model using seven HLPGs effectively predicts patient outcomes and identifies potential immunotherapy targets like ITLN1.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Hypoxia and lipid metabolism are critical in colorectal cancer (CRC) progression.
  • The precise roles of hypoxia- and lipid metabolism-related genes (HLPG) in CRC and their prognostic value are not fully understood.

Purpose Of The Study

  • To identify key HLPGs in CRC.
  • To develop a prognostic risk model based on HLPGs.
  • To explore the functional roles of specific HLPGs in CRC and their potential as immunotherapy targets.

Main Methods

  • Differential gene expression analysis using TCGA-COAD and GEO databases.
  • Univariate Cox regression and consensus clustering for subtype identification.
  • Development and validation of a seven-gene risk scoring model.
  • Functional validation of ITLN1 and SFRP2 in CRC cell lines.

Main Results

  • 117 HLPGs were identified, with 17 showing prognostic relevance.
  • Two distinct CRC molecular subtypes were discovered, differing in immune microenvironment and survival.
  • The seven-HLPG risk model accurately stratified patients into high- and low-risk groups.
  • SFRP2 and ITLN1 were confirmed to influence CRC cell proliferation, migration, and epithelial-mesenchymal transition (EMT).
  • ITLN1 was found to upregulate PD-L1, enhancing immunotherapy sensitivity.

Conclusions

  • HLPGs are closely linked to CRC prognosis, and a seven-gene signature can predict patient outcomes.
  • ITLN1 and SFRP2 play significant roles in CRC progression and may serve as therapeutic targets.
  • ITLN1 presents a potential target for improving immunotherapy response in CRC patients.

Keywords:

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