Elevated expression of ASCL2 is an independent prognostic indicator in lung squamous cell carcinoma

J Clin Pathol. 2016 Apr;69(4):313-8. doi: 10.1136/jclinpath-2015-203025. Epub 2015 Oct 19.

Abstract

Aims: ASCL2, a basic helix-loop-helix (bHLH) transcription factor, is putatively involved in tumour progression. This study aimed to evaluate ASCL2 expression level in non-small-cell carcinoma (NSCLC) and assess its prognostic value for patients.

Methods: ASCL2 protein expression was detected by immunohistochemistry (IHC cohort) in 79 cases of squamous cell carcinoma (SCC) and 67 cases of adenocarcinoma (AC). Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of ASCL2. The same analyses were conducted in a cohort (n=790) from The Cancer Genome Atlas database (TCGA) to validate the expression pattern and prognostic value of ASCL2.

Results: ASCL2 expression levels were significantly increased in SCC compared with normal lung tissue (p<0.001) and AC (p=0.008). High ASCL2 expression was associated with advanced tumour-node-metastasis (TNM) stage (p=0.023) and worse differentiation status (p=0.001) in SCC, but a positive correlation between ASCL2 expression level and advanced TNM stage (p=0.016) was observed in AC. Kaplan-Meier analysis showed that ASCL2 was prognostic in SCC (p=0.004) but not in AC (p=0.183). Multivariable Cox regression analysis indicated that elevated expression of ASCL2 was an independent prognostic factor (HR 2.764; p=0.030) in SCC patients. The expression pattern and prognostic significance of ASCL2 in SCC and AC were validated using the TCGA cohort.

Conclusions: Elevated expression of ASCL2 may identify an aggressive subgroup in SCC and serve as an independent prognostic indicator in these patients.

Keywords: CANCER RESEARCH; HISTOPATHOLOGY; LUNG CANCER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Basic Helix-Loop-Helix Transcription Factors / analysis
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis

Substances

  • ASCL2 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor