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Systematic Analysis of the Prognostic Significance and Roles of the Integrin Alpha Family in Non-Small Cell Lung Cancers

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Abstract

Introduction

Lung cancer is one of the most common cancer malignancies and the principal cause of cancer-associated deaths worldwide. Non-small cell lung cancers (NSCLCs) account for more than 80% of all lung cancer cases. Recent studies showed that the genes of the integrin alpha (α) (ITGA) subfamily play a fundamental role in various cancers. However, little is known about the expression and roles of distinct ITGA proteins in NSCLCs.

Methods

Gene Expression Profiling Interactive Analysis and UALCAN (University of ALabama at Birmingham CANcer) web resources and The Cancer Genome Atlas (TCGA), ONCOMINE, cBioPortal, GeneMANIA, and Tumor Immune Estimation Resource databases were used to evaluate differential expression, correlations between the expression levels of individual genes, the prognostic value of overall survival (OS) and stage, genetic alterations, protein–protein interactions, and the immune cell infiltration of ITGAs in NSCLCs. We used R (v. 4.0.3) software to conduct gene correlation, gene enrichment, and clinical correlation of RNA sequencing data of 1016 NSCLCs from TCGA. To evaluate the expression of ITGA5/8/9/L at the expression and protein levels, qRT-PCR, immunohistochemistry (IHC), and hematoxylin and eosin (H&E) were performed, respectively.

Results

Upregulated levels of ITGA11 messenger RNA and downregulated levels of ITGA1/3/5/7/8/9/L/M/X were observed in the NSCLC tissues. Lower expression of ITGA5/6/8/9/10/D/L was discovered to be expressively associated with advanced tumor stage or poor patient prognosis in patients with NSCLC. A high mutation rate (44%) of the ITGA family was observed in the NSCLCs. Gene Ontology functional enrichment analyses results revealed that the differentially expressed ITGAs could be involved in roles related to extracellular matrix (ECM) organization, collagen-containing ECM cellular components, and ECM structural constituent molecular functions. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that ITGAs may be involved in focal adhesion, ECM–receptor interaction, and amoebiasis; the expression of ITGAs was significantly correlated with the infiltration of diverse immune cells in NSCLCs. ITGA5/8/9/L was also highly correlated with PD-L1 expression. The validation results for marker gene expression in NSCLC tissues by qRT-PCR, IHC, and H&E staining indicated that the expression of ITGA5/8/9/L decreased compared with that in normal tissues.

Conclusion

As potential prognostic biomarkers in NSCLCs, ITGA5/8/9/L may fulfill important roles in regulating tumor progression and immune cell infiltration.

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Acknowledgements

We are particularly grateful to all the people who have given us help with our article.

Funding

This work was supported by the Performance incentives guide special key project of Chongqing scientific research institutes (cstc2019jxj1130005, Yuequan Jiang) and the Laboratory opening fund of Chongqing University Cancer Hospital (Fei Teng). The Rapid Service Fee was funded by the authors.

Author Contributions

Yu Huang and Dong-Ming Guo conceived the idea and conceptualized the study. Shi Bu and Wei Xu collected the data and analyzed the data. Qing-Chun Cai and Jian Xu drafted the manuscript, then Yue-Quan Jiang and Fei Teng reviewed the manuscript. All authors read and approved the final draft.

Disclosures

Yu Huang, Dong-Ming Guo, Shi Bu, Wei Xu, Qing-Chun Cai, Jian Xu, Yue-Quan Jiang and Fei Teng have nothing to disclose.

Compliance with Ethics Guidelines

The data has been taken from the ONCOMINE database, the Gene Expression Profiling Interactive Analysis web resource, The Cancer Genome Atlas (TCGA) database, the UALCAN web resource, the cBioPortal database, the GeneMANIA database, and the Tumor Immune Estimation Resource database. IRB approval was not required as all the database information in the article was publicly available without any limitation and data was deidentified.

Data Availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Yu Huang and Dong-Ming Guo contributed equally to this study.

Authors and Affiliations

  1. School of Medicine, Chongqing University, Chongqing, 400030, China

    Yu Huang

  2. Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, No. 181 of Hanyu Road, Shapingba District, Chongqing, 400030, China

    Yu Huang, Dong-Ming Guo, Shi Bu, Wei Xu, Qing-Chun Cai, Jian Xu, Yue-Quan Jiang & Fei Teng

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  1. Yu Huang
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Huang, Y., Guo, DM., Bu, S. et al. Systematic Analysis of the Prognostic Significance and Roles of the Integrin Alpha Family in Non-Small Cell Lung Cancers. Adv Ther 40, 2186–2204 (2023). https://doi.org/10.1007/s12325-023-02469-2

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