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. 2024 Mar 30;73(5):85.
doi: 10.1007/s00262-024-03672-y.

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

Zihao Niu  1   2 , Peng Sun  1   3 , Mark E Zafereo  1 , Hongliang Liu  4 , Peng Wei  5 , Jia Wu  6 , Neil D Gross  1 , Sanjay Shete  5   7 , Qingyi Wei  4 , Guibin Zheng  1   8 , Andy G Sikora  1 , George A Calin  9 , Guojun Li  10   11
Affiliations

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

Zihao Niu et al. Cancer Immunol Immunother. .

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; Smoking-related head and neck cancer; Survival biomarkers; microRNA binding site.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The OS, DSS, and DFS in all patients with smoking-related head and neck cancer (N = 1403) by (A) OS estimated for TGF-β1 rs1800470 genotype, (B) DSS estimated for TGF-β1 rs1800470 genotype, and (C) DFS estimated for TGF-β1 rs1800470 genotype
Fig. 2
Fig. 2
The OS, DSS, and DFS in all patients with smoking-related head and neck cancer (N = 1403) by (A) OS estimated for TGF-βR1 rs334348 genotype, (B) DSS estimated for TGF-βR1 rs334348 genotype, and (C) DFS estimated for TGF-βR1 rs334348 genotype
Fig. 3
Fig. 3
The OS, DSS, and DFS by the combined genotypes of the 2 polymorphisms in all patients with smoking-related head and neck cancer (N = 1403). (A): OS; (B): DSS; and (C): DFS, respectively
Fig. 4
Fig. 4
The OS, DSS, and DFS by TGF-β1 rs1800470 and TGF-βR1 rs334348 genotypes in the patients with smoking-related head and neck cancer from TCGA (N = 312). (A) OS estimated for TGF-β1 rs1800470 genotype, (B) DFS estimated for TGF-β1 rs1800470 genotype, (C) OS estimated for TGF-βR1 rs334348 genotype, and (D) DFS estimated for TGF-βR1 rs334348 genotype
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