Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

Strahlenther Onkol. 2021 Mar;197(3):231-245. doi: 10.1007/s00066-020-01653-5. Epub 2020 Jun 25.

Abstract

Purpose: Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts.

Methods: This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI‑1, and CD44).

Results: In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI‑1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI‑1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis.

Conclusion: Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.

Keywords: Head and neck cancer; Molecular markers; Primary radiochemotherapy; Surgical treatment; Survival.

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase 1 Family / analysis*
  • Female
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Hyaluronan Receptors / analysis*
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / pathology*
  • Polycomb Repressive Complex 1 / analysis*
  • Prognosis
  • Repressor Proteins / analysis*
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / diagnosis*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Survival Analysis
  • Tumor Suppressor Proteins / analysis*

Substances

  • BCL11B protein, human
  • BMI1 protein, human
  • CD44 protein, human
  • Hyaluronan Receptors
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Aldehyde Dehydrogenase 1 Family
  • Polycomb Repressive Complex 1