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.
ABSTRACT
Objective: To evaluate the efficacy and safety of Bevacizumab (BEV) combined with first-generation EGFR-TKI versus first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone in the first-line treatment of EGFR-mutated positive (EGFRm) advanced non-small cell lung cancer(NSCLC). Methods: PubMed, Cochrane Library, Embase, Weipu chinese journal, China Biology Medicine database, China National Knowledge Infrastructure and Wanfang relevant databases were searched to collect randomized controlled trials (RCTs) of BEV combined with first-generation EGFR-TKI (experimental group) versus first-generation EGFR-TKI alone (control group) in the first-line treatment of EGFRm advanced NSCLC from database foundation to July, 2019. The data in the included RCTs were extracted, and the qualities were assessed in accordance with Cochrane Collaboration, and a Meta-analysis was conducted with RevMan 5.3 software, Risk ratio (RR), hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 7 RCTs were enrolled, including 834 patients. The results of meta-analysis showed that experimental group was better than control group in objective response rate (ORR) (RR = 1.27, 95% CI: 1.15-1.41, P < 0.000 01), disease control rate (DCR) (RR = 1.10, 95% CI: 1.02-1.20, P = 0.02) and progression-free survival (PFS) (HR = 0.57, 95% CI: 0.44-0.75, P < 0.000 1) in terms of efficacy. In terms of safety, the incidences of hypertension (RR = 4.11, 95% CI: 2.95-5.93, P < 0.000 01], proteinuria (RR = 5.16, 95% CI: 3.40-7.83, P < 0.000 01), hemorrhage (RR = 3.34, 95% CI: 2.37-4.72, P<0.000 01) were higher in experimental group. There was no significant difference between the two groups in the incidences of rash (RR = 1.00, 95% CI: 0.92-1.08, P = 0.91), diarrhea (RR=1.05, 95% CI: 0.91-1.21, P = 0.52), hypohepatia (RR = 0.91, 95% CI: 0.72-1.14, P = 0.42). Conclusion: BEV combined with first-generation EGFR-TKI significantly improve ORR, DCR and PFS in the first-line treatment of EGFRm advanced NSCLC, but also increase the risks of hypertension, proteinuria and hemorrhage.