Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma

Paolo Boscolo-Rizzo,Silvia Giunco,Maria Cristina Da Mosto,Jerry Polesel,Luigia Bandolin,Monica Mantovani,Giacomo Spinato,Annarosa Del Mistro,Daniele Borsetto,Marco Stellin,Giancarlo Tirelli,Anna Menegaldo,Jonathan Fussey,Enrica Rampazzo,Anita De Rossi

doi:10.1038/s41598-019-54028-x

Abstract

A growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability.

Highlights

To date, there are no robust molecular markers useful in planning management for patients with head and neck squamous cell carcinoma (HNSCC) and, despite their intrinsic heterogeneity, all HNSCCs are treated[1]
These observations have raised several questions: are shortened telomeres in surrounding the tumor (SM) the consequence of greater cell proliferation or are they linked to an individual’s constitutive telomere length? What is the significance of telomere length in peripheral blood mononuclear cells (PBMC)? What is the significance of cell-free circulating plasma TERT mRNA? To answer these questions, in this new prospective study, we collected blood samples in addition to cancer tissue and normal SM
Data from this study confirm our previous observation, obtained from an independent series of patients[13], that short telomeres in histologically normal SM are independently associated with a higher risk of mucosal failure

Summary

Introduction

There are no robust molecular markers useful in planning management for patients with HNSCC and, despite their intrinsic heterogeneity, all HNSCCs are treated[1]. Our previous research has demonstrated high TERT levels in cancer tissues to be associated with progression at regional and distant sites and higher risk of death, and short telomeres in the mucosa surrounding the tumor (SM) to predict a higher risk of mucosal failure[13]. These observations have raised several questions: are shortened telomeres in SM the consequence of greater cell proliferation or are they linked to an individual’s constitutive telomere length? We estimated telomere length and TERT levels and their relationship in cancer tissue, SM, and peripheral blood, and we investigated their predictive and prognostic roles in patients with HNSCC

Methods

Results

Conclusion