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Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways
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-S...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sciendo
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802404/ https://www.ncbi.nlm.nih.gov/pubmed/35136724 http://dx.doi.org/10.2478/jtim-2021-0046 |
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author | Wang, Yizhe Hou, Kezuo Jin, Yue Bao, Bowen Tang, Shiying Qi, Jianfei Yang, Yang Che, Xiaofang Liu, Yunpeng Hu, Xuejun Zheng, Chunlei |
author_facet | Wang, Yizhe Hou, Kezuo Jin, Yue Bao, Bowen Tang, Shiying Qi, Jianfei Yang, Yang Che, Xiaofang Liu, Yunpeng Hu, Xuejun Zheng, Chunlei |
author_sort | Wang, Yizhe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8802404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Sciendo |
record_format | MEDLINE/PubMed |
spelling | pubmed-88024042022-02-07 Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways Wang, Yizhe Hou, Kezuo Jin, Yue Bao, Bowen Tang, Shiying Qi, Jianfei Yang, Yang Che, Xiaofang Liu, Yunpeng Hu, Xuejun Zheng, Chunlei J Transl Int Med Original Article 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. Sciendo 2021-12-31 /pmc/articles/PMC8802404/ /pubmed/35136724 http://dx.doi.org/10.2478/jtim-2021-0046 Text en © 2021 Yizhe Wang et al., published by Sciendo https://creativecommons.org/licenses/by-nc-nd/3.0/This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. |
spellingShingle | Original Article Wang, Yizhe Hou, Kezuo Jin, Yue Bao, Bowen Tang, Shiying Qi, Jianfei Yang, Yang Che, Xiaofang Liu, Yunpeng Hu, Xuejun Zheng, Chunlei Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title | Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title_full | Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title_fullStr | Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title_full_unstemmed | Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title_short | Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
title_sort | lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802404/ https://www.ncbi.nlm.nih.gov/pubmed/35136724 http://dx.doi.org/10.2478/jtim-2021-0046 |
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