SOX4, SOX11 and PAX6 mRNA expression was identified as a (prognostic) marker for the aggressiveness of neuroendocrine tumors of the lung by using next-generation expression analysis (NanoString)

Future Oncol. 2015;11(7):1027-36. doi: 10.2217/fon.15.18.

Abstract

Background: Neuroendocrine tumors of the lung (NELC) account for 25% of all lung cancer cases and transcription factors may drive dedifferentiation of these tumors. This study was conducted to identify supportive diagnostic and prognostic biomarkers.

Materials & methods: A total of 16 TC, 13 AC, 16 large cell neuroendocrine carcinomas and 15 small cell lung cancer were investigated for the mRNA expression of 11 transcription factors and related genes (MYB, MYBBP1A, OCT4, PAX6, PCDHB, RBP1, SDCBP, SOX2, SOX4, SOX11, TEAD2).

Results: SOX4 (p = 0.0002), SOX11 (p < 0.0001) and PAX6 (p = 0.0002) were significant for tumor type. Elevated PAX6 and SOX11 expression correlated with poor outcome in large cell neuroendocrine carcinomas and small cell lung cancer (p < 0.0001 and p = 0.0232, respectively) based on survival data of 34 patients (57%).

Conclusion: Aggressiveness of NELC correlated with increasing expression of transcription factors. SOX11 seems to be a highly valuable diagnostic and prognostic marker for aggressive NELC.

Keywords: NanoString nCounter; carcinoids; large cell lung cancer; lung cancer; mRNA; neuroendocrine; small cell lung cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Eye Proteins / genetics*
  • Gene Expression Profiling / methods
  • Homeodomain Proteins / genetics*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lymphatic Metastasis
  • Middle Aged
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics*
  • SOXC Transcription Factors / genetics*

Substances

  • Biomarkers, Tumor
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Repressor Proteins
  • SOX11 protein, human
  • SOX4 protein, human
  • SOXC Transcription Factors