TGF-β1 and TGF-βR1 Variants Are Associated With Clinical Outcomes in Smoking-Related Head and Neck Cancer Patients Treated With Chemoradiation Through Modulating microRNA-Mediated Regulation

Authors

Zihao Niu
Peng Sun
Mark E Zafereo
Hongliang Liu
Peng Wei
Jia Wu
Neil D Gross
Sanjay Shete
Qingyi Wei
Guibin Zheng
Andy G Sikora
George A Calin
Guojun Li

Publication Date

3-30-2024

Journal

Cancer, Immunology, Inmunotherapy

Abstract

TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or CC genotype had 30–35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-βR1 rs334348 GA or GG genotype had significant 50–60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60–70%. The TCGA dataset was used for validation. These findings suggest that TGF-β1 rs1800470 and TGF-βR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life.

Keywords

TGF-β-related genetic variants, Smoking status, microRNA binding site, Smoking-related head and neck cancer, Survival biomarkers

Comments

PMID: 38554185