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

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.

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B, BMI-1, and CD44 in Different Tissues of HNSCC Patients

“…As a histopathological reference regarding the immunoexpression of the markers in formalin-fixed, paraffin-embedded samples, we compared samples of this manuscript to the HNSCC tumor tissue micro assays of the Göttingen cohorts of our former manuscript [ 20 ]. For quality control reasons and to identify tumor infiltrates in the HNSCC and LN tissues, we performed hematoxylin/eosin stainings of the samples without the IHC markers as well as control stainings with mouse pre-immune serum and the IHC secondary antibodies alone instead of specific antibodies and secondary antibodies to exclude unspecific staining.…”

“…In a cohort of advanced-stage HNSCC patients treated with primary radio(chemo)therapy, CSC markers had a differential influence on survival, while HPV status had no significant influence. Of the CSC markers, BMI-1 and CD44 indicated a significantly worse prognosis on survival, while ALDH1 and BCL11B appear to have protective properties for HNSCC survival [ 20 ].…”

Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer

“… Chen et al (2014) suggested that CD44 is related to worse T category, N category, tumor grade and prognosis in pharyngeal and laryngeal cancer, but no clear association was revealed between CD44 expression and oral cancer. Jakob et al (2020) recommend testing for CSC markers in patients with advanced or late stage HNSCC, as they observed correlations between CSC markers ALDH1, BCL11B, BMI-1, and CD44 and prognosis.…”

HPV+ve/−ve oral-tongue cancer stem cells: A potential target for relapse-free therapy

“…CSCs were first isolated and recognized in 1990 in leukemia using two stemness markers CD34+ and CD38 [40] . Subsequently, CSCs expressing various cell surface markers including CD133, CD44, ALDH, BMI-1, SOX2, OCT-4, nestin and NANOG, have been identified in several solid and non-solid tumors including TSCCs [ 39 , [41] , [42] , [43] , [44] ]. These rare population (1–2%) of CSCs or progenitor cancer cells manifest specific stemness properties with a capability to form new tumor following self-renewal show multi-drug resistance and progressive metastasis and recurrence of tumor ( Fig.…”