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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
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Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer

Ji Yeon Kim1, Woo Jeong Lee2, Ha Young Park3

  • 1Department of Pathology, Inje University Haeundae Paik Hospital, Busan, Korea.

Journal of Pathology and Translational Medicine
|August 18, 2018
PubMed
Abstract

Insights

MicroRNAs (miRNAs) are deregulated in non-small cell lung cancer (NSCLC). This study found miR-1, miR-124, and miR-196a are overexpressed in EGFR T790M-mutated NSCLC resistant to tyrosine kinase inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • Aberrant miRNA expression is implicated in various cancers, including non-small cell lung cancer (NSCLC).
  • Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant clinical challenge in NSCLC, often associated with the T790M mutation.

Purpose of the Study:

  • To investigate the differential expression of miRNAs in NSCLC with the EGFR T790M mutation.
  • To identify specific miRNAs associated with resistance to EGFR TKIs in NSCLC.

Main Methods:

  • Analysis of miRNA expression profiles in six cases of resected NSCLC harboring the T790M mutation.
  • Comparison of miRNA expression using miRNA polymerase chain reaction (PCR) array profiling between EGFR T790M-mutated and L858R-mutated NSCLC.
  • Validation of differentially expressed miRNAs using quantitative real-time PCR (qRT-PCR).

Main Results:

  • miRNA PCR array profiling identified three miRNAs (miR-1, miR-196a, miR-124) with significantly altered expression (≥4.0-fold change) in the T790M group compared to the L858R group.
  • Validation by qRT-PCR confirmed the overexpression of miR-1, miR-196a, and miR-124 in the T790M-mutated NSCLC.
  • miR-1 and miR-124 showed particularly significant overexpression in the T790M group (p < 0.01).

Conclusions:

  • MiR-1, miR-124, and miR-196a are significantly overexpressed in EGFR T790M-mutated NSCLC.
  • These miRNAs may play a role in the development of resistance to EGFR TKIs in NSCLC.
  • Further investigation into the functional roles of these miRNAs could offer potential therapeutic targets.
Keywords:
EGFR T790M mutationLung neoplasmsMicroRNAs

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