Elevated LSD1 and SNAIL Expression Indicate Poor Prognosis in Hypopharynx Carcinoma

Int J Mol Sci. 2022 May 3;23(9):5075. doi: 10.3390/ijms23095075.

Abstract

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.

Keywords: IHC; LSD1; SNAIL; biomarker; co-expression; head and neck squamous cell carcinoma (HNSCC).

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Head and Neck Neoplasms* / diagnosis
  • Head and Neck Neoplasms* / genetics
  • Histone Demethylases* / genetics
  • Histone Demethylases* / metabolism
  • Humans
  • Hypopharyngeal Neoplasms* / diagnosis
  • Hypopharyngeal Neoplasms* / genetics
  • Hypopharynx / pathology
  • Neoplasm Recurrence, Local
  • Prognosis
  • Snail Family Transcription Factors* / genetics
  • Snail Family Transcription Factors* / metabolism
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • Biomarkers, Tumor
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Histone Demethylases
  • KDM1A protein, human