Abstract
Objective
To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms.
Methods
LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exogenous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR, Ak, and Erk.
Results
The disease control rate according to LN5 mRNA level was 52.9% for the below cutpoint group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib.
Conclusion
Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.
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Supported by grants from the National Natural Science Foundation of China (No. 30772531), Guangdong Provincial Medical Science and Technology Research Foundation (No. B2006001) and China Postdoc toral Science Foundation (No. 20060400212).
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An, S., Zhu, J., Chen, Z. et al. Elevated expression level of laminin 5 may be a negative predictive factor for the response to gefitinib in lung cancer patients. Chin. -Ger. J. Clin. Oncol. 7, 677–681 (2008). https://doi.org/10.1007/s10330-008-0140-x
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DOI: https://doi.org/10.1007/s10330-008-0140-x