TY - JOUR
T1 - 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
AU - Niu, Zihao
AU - Sun, Peng
AU - Zafereo, Mark E.
AU - Liu, Hongliang
AU - Wei, Peng
AU - Wu, Jia
AU - Gross, Neil D.
AU - Shete, Sanjay
AU - Wei, Qingyi
AU - Zheng, Guibin
AU - Sikora, Andy G.
AU - Calin, George A.
AU - Li, Guojun
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - Smoking status
KW - Smoking-related head and neck cancer
KW - Survival biomarkers
KW - TGF-β-related genetic variants
KW - microRNA binding site
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U2 - 10.1007/s00262-024-03672-y
DO - 10.1007/s00262-024-03672-y
M3 - Article
C2 - 38554185
AN - SCOPUS:85188914612
SN - 0340-7004
VL - 73
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 5
M1 - 85
ER -