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Downregulated CDH3 is correlated with a better prognosis for LUAD and decreases proliferation and migration of lung cancer cells

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Abstract

Background

CDH3 is a glycoprotein with a single-span transmembrane domain that mediates cell-to-cell adhesion. Abnormal expression of CDH3 is associated with a poor prognosis in patients with breast, thyroid, colorectal carcinomas and glioblastoma. Soluble CDH3 in pleural effusions can be used as a marker for real-time monitoring of resistance to first- and second-generation EGFR-TKIs. The CDH3 mechanism underlying lung adenocarcinomas (LUADs) has not been established.

Objective

This study analyzed the correlation between CDH3 expression and lung cancer prognosis and the effect of down-regulation CDH3 expression on the proliferation and migration of lung cancer cells.

Methods

CDH3 expression was studied using the Oncomine, TIMER, PanglaoDB, and GEPIA databases. The effect of CDH3 on clinical prognosis was assessed with GEPIA, the PrognoScan database, and Kaplan–Meier plotter. The relationship between CDH3 to immune infiltrating cells was explored using TIMER and TISIDB. The function of CDH3 in lung cancer cell lines was determined by CCK-8 and wound healing assays in vitro. Furthermore, RNA sequencing was used to identify key signaling pathways and differentially-expressed genes.

Results

LUAD tissues had higher CDH3 expression compared with normal tissues and were associated with worse overall survival in patients with LUAD. CDH3 expression had positive associations with infiltration of CD4 + T cells, Tregs and exhausted T cells, but negative associations with infiltration of B cells in patients with LUAD. CCK-8 and wound healing assays revealed that downregulation of CDH3 inhibited the proliferation and migration of cells. KEGG analysis revealed that the TGF-beta signaling pathways were demonstrated to be enriched pathways for genes negatively regulated by knockdown of CDH3.

Conclusion

CDH3 expression affects proliferation and migration of lung cancer cells and might serve as a potential prognostic marker in LUAD patients.

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Acknowledgements

We would like to thank Nan Ding from Beijing Cancer Hospital for helpful suggestions. We also would like to express their gratitude to EditSprings (https://www.editsprings.cn) for the expert linguistic services provided.

Funding

This study was supported by the National Natural Science Foundation of China (no. 82103289).

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Authors and Affiliations

  1. Department of Blood Transfusion, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Da Hua Road, Dong Dan, Beijing, 100730, People’s Republic of China

    Wanru Ma & Junhua Hu

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  1. Wanru Ma
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  2. Junhua Hu
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WM designed the research and wrote the manuscript. JH reviewed the manuscript.

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Correspondence to Junhua Hu.

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Ma, W., Hu, J. Downregulated CDH3 is correlated with a better prognosis for LUAD and decreases proliferation and migration of lung cancer cells. Genes Genom (2023). https://doi.org/10.1007/s13258-023-01476-5

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