Functional Genetic Variants in TGFβ1 and TGFβR1 in miRNA-Binding Sites Predict Outcomes in Patients with HPV-positive Oropharyngeal Squamous Cell Carcinoma

Abstract

Purpose:TGF-β1 and TGF-βR1 participate in regulation of the host’s immune system and inflammatory responses and may serve as prognostic biomarkers for HPV-associated OPSCC. Experimental Design: This study included 1013 patients with incident OPSCC, of whom 489 had tumor HPV16 status determined. All patients were genotyped for two functional polymorphisms: TGF-β1 rs1800470 and TGF-βR1 rs334348. Univariate and multivariate Cox regression models were performed to evaluate associations between the polymorphisms and OS, DSS, and DFS. Results: Patients with TGF-β1rs1800470 CT or CC genotype had significantly 70%-80% reduced risks of OS, DSS, and DFS compared with patients with TT genotype, and patients with TGF-βR1rs334348 GA or GG genotype had significantly 30%-40% reduced risks of OS, DSS, and DFS compared with patients with AA genotype. Furthermore, among patients with HPV-positive OPSCC, the same patterns were observed but the risk reductions were greater: up to 80%-90% for TGF-β1rs1800470 CT or CC genotype and 70%-85% for TGF-βR1rs334348 GA or GG genotype. The risk reductions were greater still, up to 17-25 times reduced, for patients with both TGF-β1rs1800470 CT or CC genotype and TGF-βR1rs334348 GA or GG genotype compared to patients with both TGF-β1rs1800470 TT genotype and TGF-βR1rs334348 AA genotype among patients with HPV-positive OPSCC. Conclusions: Our findings indicate that TGF-β1rs1800470 and TGF-βR1rs334348 may individually or jointly modify risks of death and recurrence in patients with OPSCC, particularly those with HPV-positive OPSCC patients undergoing definitive radiotherapy, and may serve as prognostic biomarkers, which could lead to better personalized treatment and improved prognosis.

A novel CAF-cancer cell crosstalk-related gene prognostic index based on machine learning: prognostic significance and prediction of therapeutic response in head and neck squamous cell carcinoma

“…As shown in Additional file 1 : Figure S3B, the HPV-positive group had significantly lower content of MatCAF. It has been indicated that HPV-positive HSNCC patients [ 35 , 36 ] and those with low stroma abundance [ 37 , 38 ] have a better prognosis. MatCAF is an important cell for stroma production, so a low level of MatCAF may be one of the reasons why HPV-positive patients have a better prognosis.…”

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

“…According to Xiao Y et al [58], the T allele of variant rs1800470 (CT/TT) is associated with the risk of developing radiation-induced pneumonia in patients with esophageal squamous cell carcinoma. In patients with oropharyngeal squamous cell carcinoma undergoing radiotherapy, the presence of the rs1800470 variant of TGFβ1 may reduce and modify the risk of death and recurrence [59].…”

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

“…Findings also suggest the potential involvement of these single nucleotide polymorphisms in the predisposition to and progression of specific diseases, underscoring the prospective clinical relevance of these genetic variants [ 20 , 21 ]. Notably, our most recent study suggested that both TGF-β1 rs1800470 and TGF-βR1 rs334348 might significantly affect the survival of patients with human papillomavirus (HPV)-associated oropharyngeal cancer [ 22 ], while it remains unknown whether the same genetic variants of TGF-β1 and TGF-βR1 impact the clinical outcomes of smoking-related head and neck cancer. Since these two functionally significant genetic variants of TGF-β1 and TGF-βR1 operate within the same pathway, it may allow us to evaluate the comprehensive impact of TGF-β1 rs1800470 and TGF-βR1 rs334348 on survival of smoking-related head and neck cancer [ 23 ].…”