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Updated: Jul 27, 2025

Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
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.
Abstract:
The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from The Cancer Genome Atlas. By applying ESTIMATE and ssGSEA, KRAS-mutated group was discovered to be associated with lower immune infiltration, lower expression of immune checkpoints, especially, a lower abundance of B cell, CD8+ T cell, dendritic cell, natural killer cell, and macrophage, higher abundance of neutrophil and endothelial cell. Through ssGSEA, we found that the process of antigen-presenting cell co-inhibition and co-stimulation were inhibited, cytolytic activity and human leukocyte antigen molecules were downregulated in the KRAS-mutated group. And KRAS mutation is negatively related to antigen presentation and procession, cytotoxic lymphocyte activity, cytolytic activities, and cytokine interaction signaling pathway via gene function enrichment analysis. Finally, 24 immune-related genes were identified to establish an immune-related gene signature with excellent prognostic prediction capacity, whose 1-, 3- and 5-year AUCs were 0.893, 0.986, and 0.999. Our findings elucidate the features of the immune landscape of KRAS-mutated groups and successfully established a prognostic signature on the basis of immune-related genes in LUAD.
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.
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