Plasma MiRNA alterations between NSCLC patients harboring Del19 and L858R EGFR mutations

Abstract

Based on recognition of driver mutations, treatment paradigm for non-small-cell lung cancer (NSCLC) patients has been shifted. However, recently exon 19 deletion mutation (del19) of epidermal growth factor receptor (EGFR) clearly shows better clinical benefit over single-point substitution mutation L858R in exon 21 (L858R). The aim of this study was to investigate the difference by analyzing the expression of plasma microRNAs (miRNAs) of NSCLC patients with EGFR mutation del19 or L858R. MiRNA microarray of plasma from patients' blood identified 79 mapped, network-eligible miRNAs (fold > 5), of which 76 were up regulated and 3 were down regulated. Genetic network was performed with Ingenuity Pathway Analysis (IPA). Among analysis, MYC, Argonaute2 (AGO2), Y-box binding protein 1 (YBX1), cyclin E1 (CCNE1) were involved in organismal abnormalities and cancer. Our findings provide information on the epigenetic signature of the two major sensitive mutations among NSCLC and add to the understanding of mechanisms underlying the different outcomes.

Keywords: EGFR; NSCLC; circulating miRNA; microarray; response.

Figure 1. Interrelated networks of genes and miRNAs whose expression was different between del19 and L858R mutations

In total, three important networks of interrelated miRNAs and target genes were identified. The three networks were merged by overlapping miRNAs.

Figure 2. Validation of selected candidate differentially expressed miRNAs using qRT-PCR

The results of transcriptional expression were normalized to the value of internal control (cel-mir-39). The relative expression was shown as mean ± SD. *Statistical significance of differences was analyzed by Student's test (p < 0.05).