Circulating plasma lncRNAs as novel markers of EGFR mutation status and monitors of epidermal growth factor receptor-tyrosine kinase inhibitor therapy

Abstract

Background: Epidermal growth factor receptor (EGFR) gene mutations predict tumor response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, even patients with EGFR-sensitive mutations in NSCLC have limited efficacy with EGFR-TKI. Studies have shown that long noncoding RNA (lncRNA) is related to diagnosis and prognosis with NSCLC. This study aimed to explore the correlation between lncRNA in NSCLC patients with EGFR mutation status and EGFR-TKI efficacy. Methods: The amplification-refractory mutation system method was used to test the EGFR mutation status in tumor tissues and pleural effusions of NSCLC patients. Three EGFR-mutant patients and three EGFR wild-type patients were selected. Differential lncRNA was performed on the pleural effusions of the two selected groups of patients using Clariom D Human chip technology. Five lncRNAs significantly associated with EGFR mutation status were screened by FC value and GO analysis, and then evaluated by real-time quantitative polymerase chain reaction in NSCLC patients' pleural effusions. Three were further analyzed in NSCLC patients' plasma. Results: There were 61 significant differences in lncRNA between EGFR mutation-positive and wild-type patients. Among them, SCARNA7, MALAT1, NONHSAT017369, NONHSAT051892, and FTH1P2 were significantly associated with EGFR mutation status. SCARNA7, MALAT1, and NONHSAT017369 showed consistent results with plasma in pleural effusions compared to EGFR wild-type, all upregulated in the EGFR mutation group. Conclusion: This study shows that lncRNAs can be used not only as potential biomarkers for predicting the mutation status of EGFR and the efficacy of EGFR-TKI, but also for monitoring the efficacy of EGFR-TKI.