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The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma--differences in histological subtypes

Hanne A Eide1,2, Ann Rita Halvorsen3, Maria Moksnes Bjaanæs4,5

  • 1Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway. haeid@rr-research.no.

BMC Cancer
|February 10, 2016
PubMed
Abstract

Insights

Squamous cell carcinomas show higher HMGA2 expression than adenocarcinomas in non-small cell lung cancer (NSCLC). MYCN gene expression is linked to recurrence time in NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) development involves complex molecular alterations.
  • The MYCN, HMGA2, CDKN2A, and DICER1 pathway is implicated in various solid tumors and potentially in NSCLC pathogenesis.

Purpose of the Study:

  • To investigate the gene and protein expression of MYCN, HMGA2, CDKN2A, and DICER1 in NSCLC.
  • To explore the correlation between these genes, let-7 microRNAs, and clinical outcomes, specifically time to recurrence.

Main Methods:

  • Gene expression analyzed using RT-qPCR in 175 NSCLC tumor samples.
  • Microarrays used for let-7 microRNA family expression in 78 adenocarcinomas.
  • HMGA2 protein levels assessed via immunohistochemistry in 156 tumor samples.

Main Results:

  • Squamous cell carcinomas exhibited significantly higher HMGA2 mRNA and protein expression compared to adenocarcinomas.
  • Positive correlations observed between MYCN and HMGA2 mRNA, and MYCN and DICER1 mRNA expression.
  • MYCN gene expression was associated with a shorter time to recurrence in multivariate survival analyses.

Conclusions:

  • HMGA2 expression differs significantly between NSCLC histological subtypes, with higher levels in squamous cell carcinomas.
  • MYCN, HMGA2, and DICER1 expression appear interconnected, potentially influencing let-7 microRNA levels.
  • MYCN gene expression is a potential prognostic marker for time to recurrence in NSCLC.

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