Elevated expression level of laminin 5 γ2 chain may be a negative predictive factor for the response to gefitinib in lung cancer

Abstract

14664 Background: Our previous study showed that laminin 5 (LN5) mRNA level in the carcinoma tissues is associated with the histological status, cigarette smoking, and gender of the patients with lung cancer. We noticed that this subgroup is identical with the lower level of LN5 expression level. This implies that LN5 mRNA lower level may be a molecule marker for predicting gefitinib sensitivity. 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, and the overall survival were evaluated. In vitro study were carried out by adding exogenous LN5 and gefitinib to A549 lung cancer cell line, and Western- blotting was performed to investigate the phosphorylation level of EGFR, Akt, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut-point group, and 17.6% for the above cut-point (P=0.009). Survival analysis showed that there was a significant difference between below and above cut-point group of the LN5 mRNA level (P=0.0253). There is no significant difference between EGFR mRNA expression level and response to gefitinib and survival (P>0.05). The exogenous LN5 neutralized the inhibition of phospho Akt by gefitinib in vitro. Conclusions: 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. No significant financial relationships to disclose.