The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

Lingling Zu; Jinling He; Ning Zhou; Jingtong Zeng; Yifang Zhu; Quanying Tang; Xin Jin; Lei Zhang; Song Xu

doi:10.3390/jcm11216421

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

J Clin Med. 2022 Oct 29;11(21):6421. doi: 10.3390/jcm11216421.

Authors

Lingling Zu^{1

2}, Jinling He^{2

3}, Ning Zhou^{2

3}, Jingtong Zeng^{2

3}, Yifang Zhu^{2

3}, Quanying Tang^{2

3}, Xin Jin^{2

3}, Lei Zhang¹, Song Xu^{2

3}

Affiliations

¹ School of Life Sciences, Tianjin University, Tianjin 300072, China.
² Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
³ Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Abstract

Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan-Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein-protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial-mesenchymal transition (EMT) signaling.

Keywords: ITGB2; epithelial–mesenchymal transition (EMT); integrins; metastasis; non-small-cell lung cancer.

Grants and funding

This research was funded by the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-061B). The present study was funded by the National Natural Science Foundation of China (82172776), Diversified Input Project of Tianjin, National Natural Science Foundation (21JCYBJC01770), Key Project of Tianjin Lung Cancer Institute (TJLCZD2021-05), Startup Project of Tianjin Lung Cancer Institute (TJLCZJ2021-09).