Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma

Xinyi Peng1, Zhenqi Xia2,3, Yong Guo2,3

  • 1Department of Oncology, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang 325000, China.

Aging
|June 6, 2023
PubMed

Insights

KRAS mutations in lung adenocarcinoma (LUAD) are linked to reduced immune cell infiltration and suppressed immune responses. A novel 24-gene signature accurately predicts patient prognosis in LUAD.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Lung adenocarcinoma (LUAD) exhibits significant heterogeneity, impacting treatment efficacy.
  • Understanding the immune landscape in relation to specific gene mutations is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the immune microenvironment characteristics of KRAS-mutated LUAD.
  • To identify immune-related genes for prognostic prediction in LUAD.

Main Methods:

  • Analysis of LUAD samples from The Cancer Genome Atlas.
  • Application of ESTIMATE and ssGSEA algorithms for immune infiltration and function assessment.
  • Gene function enrichment analysis and development of a prognostic gene signature.

Main Results:

  • KRAS-mutated LUAD showed lower immune infiltration, reduced immune checkpoint expression, and altered immune cell abundance (e.g., decreased B cells, CD8+ T cells; increased neutrophils).
  • Antigen presentation, cytotoxic activity, and cytokine signaling pathways were impaired in KRAS-mutated LUAD.
  • A 24-gene immune signature demonstrated high accuracy in predicting 1-, 3-, and 5-year survival (AUCs: 0.893, 0.986, 0.999).

Conclusions:

  • KRAS mutation significantly shapes the immune landscape in LUAD, characterized by immune evasion.
  • The developed immune-related gene signature offers a promising tool for prognostic prediction in LUAD patients.