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.
Highlights
Being the leading cause of cancer mortality, lung cancer accounts for almost one third of all death of cancer, of which 75% are non-small-cell lung cancer (NSCLC) [1]
New statistics indicated that del19 clearly exhibited more beneficial while L858R seemed equal to chemotherapy in overall survival (OS) [8,9,10]
We investigated the global expression profile of miRNAs from NSCLC patients’ plasma using high-density miRNA microarray containing 3100 capture probes covering all human microRNAs annotated in miRBase 18.0
Summary
Being the leading cause of cancer mortality, lung cancer accounts for almost one third of all death of cancer, of which 75% are NSCLC [1]. Activating mutations in EGFR confer hypersensitivity to tyrosine kinase inhibitors (TKI) in NSCLC patients, among which del and L858R are the two major classic mutations. Both mutations are consistently associated with dramatic and usually long-lasting response to TKI [3,4,5]. Different publications reported that del seemed to have better clinical outcome than L858R [6, 7]. New statistics indicated that del clearly exhibited more beneficial while L858R seemed equal to chemotherapy in overall survival (OS) [8,9,10]. The mechanisms about the difference remain unclear up to date
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