Transcription factors CP2 and YY1 as prognostic markers in head and neck squamous cell carcinoma: analysis of The Cancer Genome Atlas and a second independent cohort

J Cancer Res Clin Oncol. 2021 Mar;147(3):755-765. doi: 10.1007/s00432-020-03482-6. Epub 2020 Dec 14.

Abstract

Purpose: The transcription factors YY1 and CP2 have been associated with tumor promotion and suppression in various cancers. Recently, simultaneous expression of both markers was correlated with negative prognosis in cancer. The aim of this study was to explore the expression of YY1 and CP2 in head and neck squamous cell carcinoma (HNSCC) patients and their association with survival.

Methods: First, we analyzed mRNA expression and copy number variations (CNVs) of YY1 and CP2 using "The Cancer Genome Atlas" (TCGA) with 510 HNSCC patients. Secondly, protein expression was investigated via immunohistochemistry in 102 patients, who were treated in the Vienna General Hospital, utilizing a tissue microarray.

Results: The median follow-up was 2.9 years (1.8-4.6) for the TCGA cohort and 10.3 years (6.5-12.8) for the inhouse tissue micro-array (TMA) cohort. The median overall survival of the TCGA cohort was decreased for patients with a high YY1 mRNA expression (4.0 vs. 5.7 years, p = 0.030, corr. p = 0.180) and high YY1-CNV (3.53 vs. 5.4 years, p = 0.0355, corr. p = 0.213). Furthermore, patients with a combined high expression of YY1 and CP2 mRNA showed a worse survival (3.5 vs. 5.4 years, p = 0.003, corr. p = 0.018). The mortality rate of patients with co-expression of YY1 and CP2 mRNA was twice as high compared to patients with low expression of one or both (HR 1.99, 95% CI 1.11-3.58, p = 0.021). Protein expression of nuclear YY1 and CP2 showed no association with disease outcome in our inhouse cohort.

Conclusion: Our data indicate that simultaneous expression of YY1 and CP2 mRNA is associated with shorter overall survival. Thus, combined high mRNA expression might be a suitable prognostic marker for risk stratification in HNSCC patients. However, since we could not validate this finding at genomic or protein level, we hypothesize that unknown underlying mechanisms which regulate mRNA transcription of YY1 and CP2 are the actual culprits leading to a worse survival.

Keywords: CP2; Head and neck squamous cell carcinoma; Prognosis; Survival; Transcription factor; YY1.

MeSH terms

  • Biomarkers, Tumor
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Databases, Genetic
  • Female
  • Gene Dosage
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Tissue Array Analysis
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • YY1 Transcription Factor / biosynthesis
  • YY1 Transcription Factor / genetics*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RNA, Messenger
  • TFCP2 protein, human
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human