Differential expression of long non-coding RNA and mRNA in patients with gefitinib-resistant lung cancer and its significance / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the expression profile change of long non-coding RNA (IncRNA) and mRNA in plasma samples before and after drug resistance of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-sensitive gene mutation treated, and to screen out RNA molecule related to gefitinib-resistance.Methods:A total of 12 NSCLC patients with EGFR-sensitive gene mutation treated by gefitinib from Xianyang Center Hospital of Shaanxi Province and Yongchuan Hospital of Chongqing Medical University from March 2015 to April 2019 were selected. Plasma samples before and after drug resistance were collected, and 6 samples in sensitive stage and 6 samples in drug-resistant stage were taken. Gene microarray was used to screen the differentially expressed lncRNA and mRNA; the biological pathway and the function of the differentially expressed mRNA were obtained by using the gene ontology (GO) function annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.Results:The microarray detection results showed that the expression profiles of lncRNA and mRNA in the plasma of NSCLC patients were different before and after gefitinib-resistance. Fold change≥2 and P < 0.05 were taken as the differential gene screening standard, finally 38 differentially expressed lncRNAs and 53 differentially expressed mRNAs were found. Compared with the sensitive stage, 18 lncRNAs were differentially up-regulated and 20 lncRNAs were down-regulated in the drug-resistant stage; the largest up-regulation lncRNA was RP1-102K2.6 (fold change was 47.31), and the largest down-regulation lncRNA was RP11-149I2.4 (fold change was 24.34). In mRNA expression microarray, compared with sensitive stage, the expressions of 29 mRNAs were up-regulated and 24 mRNAs were down-regulated in the drug-resistant stage, the largest up-regulation mRNA was CUL2 (fold change was 58.49), the largest down-regulation mRNA was CHEK2 (fold change was 23.29). GO functional analysis showed that the differentially expressed mRNA in the plasma of patients with gefitinib-resistance were enriched in the apoptosis and protein binding regulation process. KEGG analysis showed that the differentially expressed mRNA mainly targeted cancer pathway, NSCLC pathway and other pathways. Conclusion:For NSCLC patients with EGFR gene sensitive mutation, there are multiple differentially expressed lncRNAs and mRNAs in plasma before and after drug resistance, and the differential expression may play an important role in the mechanism of gefitinib resistance.