TGF-ß1 and TGF-ßR1 variants are associated with clinical outcomes in smoking-related head and neck cancer patients treated with chemoradiation through modulating microRNA-mediated regulation.

TGF-ß1 and TGF-ßR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-ß1 rs1800470 and TGF-ßR1 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-ß1 rs1800470 and TGF-ßR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-ß1 and TGF-ßR1 and survivals. Patients with TGF-ß1 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-ßR1 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-ß1 rs1800470 and TGF-ßR1 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.

Functional Genetic Variants in TGFß1 and TGFßR1 in miRNA-Binding Sites Predict Outcomes in Patients with HPV-positive Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: TGFß1 and TGFß receptor 1 (TGFßR1) participate in regulation of the host's immune system and inflammatory responses and may serve as prognostic biomarkers for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGN: This study included 1,013 patients with incident OPSCC, of whom 489 had tumor HPV16 status determined. All patients were genotyped for two functional polymorphisms: TGFß1 rs1800470 and TGFßR1 rs334348. Univariate and multivariate Cox regression models were performed to evaluate associations between the polymorphisms and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: Patients with TGFß1 rs1800470 CT or CC genotype had 70%-80% reduced risks of OS, DSS, and DFS compared with patients with TT genotype, and patients with TGFßR1 rs334348 GA or GG genotype had 30%-40% reduced risk of OS, DSS, and DFS compared with patients with AA genotype. Furthermore, among patients with HPV-positive (HPV+) OPSCC, the same patterns were observed but the risk reductions were greater: up to 80%-90% for TGFß1 rs1800470 CT or CC genotype and 70%-85% for TGFßR1 rs334348 GA or GG genotype. The risk reductions were still greater (up to 17 to 25 times reduced) for patients with both TGFß1 rs1800470 CT or CC genotype and TGFßR1 rs334348 GA or GG genotype compared with patients with both TGFß1 rs1800470 TT genotype and TGFßR1 rs334348 AA genotype among patients with HPV+ OPSCC. CONCLUSIONS: Our findings indicate that TGFß1 rs1800470 and TGFßR1 rs334348 may individually or jointly modify risks of death and recurrence in patients with OPSCC, particularly those with HPV+ OPSCC undergoing definitive radiotherapy, and may serve as prognostic biomarkers, which could lead to better personalized treatment and improved prognosis.

Prognostic roles of a novel basement membranes-related gene signature in lung adenocarcinoma.

Background: The basement membranes (BMs) are involved in tumor progression, while few comprehensive analyses to date are performed on the role of BM-related gene signatures in lung adenocarcinoma (LUAD). Thus, we aimed to develop a novel prognostic model in LUAD based on BMs-related gene profiling. Methods: The LUAD BMs-related gene profiling and corresponding clinicopathological data were obtained from the basement membrane BASE, The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases. The Cox regression and least absolute shrinkage and selection operator (LASSO) methods were used to construct a BMs-based risk signature. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were generated to evaluate the nomogram. The GSE72094 dataset was used to validate prediction of the signature. The differences in functional enrichment, immune infiltration, and drug sensitivity analyses were compared based on risk score. Results: In TCGA training cohort, 10 BMs-related genes were found, (e.g., ACAN, ADAMTS15, ADAMTS8, BCAN, etc). The signal signature based on these 10 genes was categorized into high- and low-risk groups regarding survival differences (p < 0.001). Multivariable analysis showed that the signature of combined 10 BMs-related genes was an independent prognostic predictor. Such a prognostic value of BMs-based signature in validation cohort of the GSE72094 were further verified. The GEO verification, C-index, and ROC curve showed that the nomogram had accurate prediction performance. The functional analysis suggested that BMs were mainly enriched in extracellular matrix-receptor (ECM-receptor) interaction. Moreover, the BMs-based model was correlated with immune checkpoint. Conclusion: This study identified BMs-based risk signature genes and demonstrated their ability to predict prognosis and guide personalized treatment of patients with LUAD.

Promotion of allogeneic parathyroid cell transplantation in rats with hypoparathyroidism.

BACKGROUND: This study sought to establish a rat model of hypoparathyroidism by removing the rat parathyroid glands, and compare the effects of different transplantation sites and transplantation methods using a primary culture of parathyroid cells in vitro on the hormone secretion of the model rats. METHODS: Male Sprague Dawley (SD) rats were selected for in vivo parathyroid gland removal, and rats with abnormal postoperative water intake, weight gain, parathyroid hormone (PTH), and blood calcium ion concentration were selected as transplant recipients and divided into the model group, brachioradialis muscle cell transplantation group, gelatin sponge group, and subcutaneous transplantation group. The parathyroid tissue was removed and the primary cell culture was performed in vitro using homozygous SD rats as graft donors. When the parathyroid cells were able to secrete PTH, transplantation was performed, and the postoperative recovery of the PTH function of the rats with different transplantation sites and methods were observed. RESULTS: A recipient model with low PTH was successfully established, and parathyroid progenitor cells with obvious PTH secretion were obtained. Better secretion was observed in the brachioradialis cell group compare with other groups. CONCLUSIONS: The in vitro primary cell culture of the donor parathyroid cells combined with cell transplantation significantly improved the physiological function of the hypoparathyroid rats, and could potentially replace traditional clinical brachioradialis muscle tissue transplantation.

Design and application of submental island flap to reconstruct non-circumferential defect after hypopharyngeal carcinoma resection: a prospective study of 27 cases.

BACKGROUND: This study investigated the effects of reconstruction of hypopharyngeal non-circumferential defects with a submental island flap after ablation of hypopharyngeal carcinoma. OBJECTIVES: The purpose of our study was to identify advantages and limitations of the submental flap for reconstruction of non-circumferential hypopharyngeal defects. METHODS: A total of 27 patients who had stage II-IV hypopharyngeal cancer and underwent pharyngeal reconstruction with a submental flap by the senior author in both Department of Otolaryngology Head Neck Surgery, Chinese PLA General Hospital and Department of Otolaryngology Head Neck Surgery, Beijing Friendship Hospital, Capital Medical University. RESULTS: 96.3% (26/27) cases of submental island flap survived. There were two pharyngocutaneous fistulas, one recovered spontaneously, and the other was associated with flap necrosis, underwent neck debridement and flap removal. All except for one patient had decannulation of their nasogastric tube 2 weeks postoperatively. There was no evidence of a stricture or stenosis of the laryngopharynx, nor any sign of aspiration, except for one with esophageal inlet stricture caused by radiotherapy. There were two cases of obvious paraesthesia pharynges due to beard growth at the submental flap after reconstruction. 63.0% (17/27) patients are alive and 37% (10/27) have died of disease. The 3-year survival rate is 56.3% and the 5-year survival rate is 50.0%. CONCLUSION: The submental flap reconstruction for moderately sized non-circumferential hypopharyngeal defects is a recommended treatment option.