MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) has a poor five-year survival rate of approximately 15%.
• MicroRNAs (miRNAs) are emerging gene regulators implicated in tumorigenesis.
• Aberrant miRNA expression in cancer suggests their potential as novel biomarkers.

Purpose of the Study:

• To identify dysregulated microRNAs (miRNAs) in non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS).
• To analyze the prognostic value of identified dysregulated miRNAs in NSCLC patients.

Main Methods:

• Dysregulated miRNAs were identified using NGS in paired tumor/normal tissue samples (N = 32).
• 22 differentially-expressed miRNAs were validated using quantitative real-time PCR in tumor and adjacent normal tissues (N = 178).
• Kaplan-Meier survival analysis and Cox regression were employed for multivariate analysis to identify independent prognostic biomarkers.

Main Results:

• NGS identified 39 dysregulated miRNAs in NSCLC (28 upregulated, 11 downregulated).
• High expression of both miR-21 and miR-188 was associated with shorter relapse-free survival (RFS) and overall survival (OS).
• A combined signature of miR-21 and miR-188 overexpression was confirmed as an independent prognostic marker for RFS and OS (p = 0.001 and p < 0.0001, respectively).

Conclusions:

• NGS technology effectively identifies dysregulated miRNA profiles in resectable NSCLC.
• Overexpression of miR-21 or miR-188 correlates with a negative prognosis in NSCLC.
• The combined signature of miR-21 and miR-188 may serve as a novel independent prognostic biomarker for RFS and OS.