Abstract
Purpose
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.
Methods
The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI’s efficacy in vitro.
Results
Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.
Conclusion
OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.
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Data availability
Normalized expression data of TCGA-LUAD and clinical information that supports the findings of this study is openly available in [UCSC Xena] at [https://tcga.xenah ubs.net]. Other data supporting our conclusions are available from the corresponding author upon reasonable request.
Code availability
Not applicable.
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Funding
Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund, Grant/Award Number: cxpy2019088. Zhongnan Hospital of Wuhan University Medical Science and Technology Innovation Platform Construction Support Project, Grant/Award Number: PTXM2021019.
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Q.‐W.W., Y.‐J.W., and W.‐D.H. designed and projected the study. Q.-W.W. and Y.‐J.W. performed the specific study and analyzed the results. C.‐K.S. and Z.‐X.G. helped collect specimens and patients' clinical information. Q.‐W.W., Y.‐J.W., and W.‐D.H. participated in writing the manuscript. All authors reviewed the manuscript.
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Informed consents were obtained from all subject, and this study was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University.
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Wang, YJ., Wang, QW., Yu, DH. et al. Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation. J Cancer Res Clin Oncol 147, 3245–3254 (2021). https://doi.org/10.1007/s00432-021-03731-2
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DOI: https://doi.org/10.1007/s00432-021-03731-2