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Updated: Oct 4, 2025
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Published on: May 1, 2015
Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape
Yizhe Wang1, Kezuo Hou2,3,4, Yue Jin2,3,4
1Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Background:
Inhibitors targeting integrins (ITGs) are applied as a novel strategy for cancers including lung cancer; however, the heterogeneity of ITG subunits might explain why ITG-targeted inhibitors only show limited efficacy for a small group of lung cancer patients.
Materials And Methods:
RNA-Seq data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were obtained from the TCGA database. Cox regression analysis was performed to construct the prognostic signature and generate the nomogram combined with pathologic stages (pStage). GEO datasets were used for verification. The related biological functions were analyzed by Gene Set Enrichment Analysis (GSEA) software and the TIMER database.
Results:
By Cox regression analysis of 30 ITG subunits, ITG subunit alpha 5 (ITGA5), ITG subunit alpha 6 (ITGA6), and ITG subunit alpha L (ITGAL) were identified as the prognostic factors in LUAD, which were included in the construction of a LUAD-specific 3-ITG signature. Following the calculation of risk score (RS) of each patient based on 3-ITG signature, patients with high RS in LUAD were found to exhibit worse prognosis, especially in early stage. Nomogram combined with RS and pStage could predict the prognosis of LUAD patients accurately. Mechanism exploration by GSEA showed that metastasis-related microenvironmental pathways were significantly enriched in the high-RS group. An elevated expression of ITGA5 was mainly associated with the promotion of cell migration and invasion, while the high expression of ITGAL had a strong positive correlation with the capability of recognizing and killing cancer cells.
Conclusions:
Three-ITG signature could improve the prediction ability combined with pStage in LUAD and might contribute to poor prognosis by metastasis and immune escape-related pathways.
Insights
A novel three-integrin (ITG) signature improves lung adenocarcinoma prognosis prediction. This signature, incorporating ITGA5, ITGA6, and ITGAL, identifies patients with poor outcomes linked to metastasis and immune escape.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Integrin (ITG) inhibitors are a novel cancer therapy, but their efficacy is limited in lung cancer due to ITG subunit heterogeneity.
- Understanding ITG roles is crucial for improving lung cancer treatment strategies.
Purpose of the Study:
- To develop a prognostic signature for lung adenocarcinoma (LUAD) based on integrin subunits.
- To investigate the association between the signature and patient prognosis, and explore underlying mechanisms.
Main Methods:
- RNA-Seq data from TCGA for LUAD and LUSC patients.
- Cox regression analysis to identify prognostic ITG subunits and construct a 3-ITG signature.
- Gene Set Enrichment Analysis (GSEA) for pathway enrichment and TIMER database for expression analysis.
Main Results:
- ITGA5, ITGA6, and ITGAL were identified as prognostic factors for LUAD.
- A 3-ITG signature generated a risk score (RS) where high RS correlated with worse prognosis, particularly in early-stage LUAD.
- A nomogram combining RS and pathological stage accurately predicted LUAD patient prognosis.
- GSEA revealed enrichment of metastasis and immune microenvironment pathways in the high-RS group.
- ITGA5 expression promoted cell migration/invasion, while ITGAL expression correlated with cancer cell recognition and killing.
Conclusions:
- The three-integrin (3-ITG) signature enhances prognostic prediction for LUAD when combined with pathological stage.
- The 3-ITG signature may contribute to poor prognosis through metastasis and immune escape pathways.
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