AUTHOR=Li Huakang , Xu Haoran , Guo Hong , Du Kangming , Chen Diang 

TITLE=Integrative analysis illustrates the role of PCDH7 in lung cancer development, cisplatin resistance, and immunotherapy resistance: an underlying target

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1217213

DOI=10.3389/fphar.2023.1217213

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Cisplatin resistance is a common clinical problem in lung cancer. However, the underlying mechanisms have not yet been fully elucidated, highlighting the importance of searching for biological targets.</p><p><bold>Methods:</bold> Bioinformatics analysis is completed through downloaded public data (GSE21656, GSE108214, and TCGA) and specific R packages. The evaluation of cell proliferation ability is completed through CCK8 assay, colony formation, and EdU assay. The evaluation of cell invasion and migration ability is completed through transwell and wound-healing assays. In addition, we evaluated cell cisplatin sensitivity by calculating IC<sub>50</sub>.</p><p><bold>Results:</bold> Here, we found that PCDH7 may be involved in cisplatin resistance in lung cancer through public database analysis (GSE21656 and GSE108214). Then, a series of <italic>in vitro</italic> experiments was performed, which verified the cancer-promoting role of PCDH7 in NSCLC. Moreover, the results of IC<sub>50</sub> detection showed that PCDH7 might be associated with cisplatin resistance of NSCLC. Next, we investigated the single-cell pattern, biological function, and immune analysis of PCDH7. Importantly, we noticed PCDH7 may regulate epithelial–mesenchymal transition activity, and the local infiltration of CD8<sup>+</sup> T and activated NK cells. Furthermore, we noticed that patients with high PCDH7 expression might be more sensitive to bortezomib, docetaxel, and gemcitabine, and resistant to immunotherapy. Finally, a prognosis model based on three PCDH7-derived genes (<italic>GPX8</italic>, <italic>BCAR3</italic>, and <italic>TNS4</italic>) was constructed through a machine learning algorithm, which has good prediction ability on NSCLC patients’ survival.</p><p><bold>Conclusion:</bold> Our research has improved the regulatory framework for cisplatin resistance in NSCLC and can provide direction for subsequent related research, especially regarding PCDH7.</p>