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Association between polymorphisms in microRNA target sites and survival in early-stage non-small cell lung cancer

Seung Soo Yoo1, Mi Jeong Hong2, Jang Hyuck Lee3

  • 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

Thoracic Cancer
|September 19, 2017
PubMed

Insights

Two genetic variants, POLR2A rs2071504 and NR2F6 rs2288539, are linked to survival in early-stage non-small cell lung cancer (NSCLC) patients. These findings may help predict patient prognosis after surgical resection.

Area of Science:

  • Genomics
  • Molecular Biology
  • Oncology

Background:

  • MicroRNA (miRNA) target site variants can influence gene regulation and disease outcomes.
  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, necessitating improved prognostic markers.
  • Understanding genetic associations with survival is crucial for personalized medicine in NSCLC.

Purpose of the Study:

  • To investigate the association between variants in miRNA target sites and survival outcomes in early-stage NSCLC patients.
  • To identify specific genetic markers that can predict prognosis in NSCLC.
  • To leverage high-throughput RNA-RNA interaction data for clinical relevance.

Main Methods:

  • Utilized crosslinking, ligation, and sequencing of hybrids (CLASH) data to identify RNA-RNA interactions.
  • Analyzed associations between 100 pre-selected variants in miRNA target sites and survival data from 782 early-stage NSCLC patients.
  • Employed statistical models to evaluate the impact of variants on overall survival and disease-free survival.

Main Results:

  • The POLR2A rs2071504 C > T variant was significantly associated with poorer overall and disease-free survival (HR=1.42, P=0.01; HR=1.34, P=0.01).
  • Patients with the NR2F6 rs2288539 TT genotype exhibited significantly better overall survival compared to CC or CT genotypes (HR=0.13, P=0.04).
  • Two specific variants, POLR2A rs2071504 and NR2F6 rs2288539, demonstrated a significant impact on NSCLC patient prognosis.

Conclusions:

  • POLR2A rs2071504 C > T and NR2F6 rs2288539 C > T variants are potential prognostic biomarkers for early-stage NSCLC.
  • These genetic variants may influence patient outcomes following curative surgical resection.
  • Further research can explore the functional mechanisms underlying these associations for therapeutic targeting.
Keywords:
miRNA target sitenon-small cell lung cancerpolymorphismsurvival outcome

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