scholarly journals Development and Validation of a Three-Gene-Based Prognostic Model for Predicting the Overall Survival of Head and Neck Squamous Cell Carcinoma Through Bioinformatics Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yiyuan Han ◽  
Xiaolin Cao ◽  
Xuemei Wang ◽  
Qing He

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancer worldwide and seriously threats public health safety. Despite the improvement of diagnostic and treatment methods, the overall survival for advanced patients has not improved yet. This study aimed to sort out prognosis-related molecular biomarkers for HNSCC and establish a prognostic model to stratify the risk hazards and predicate the prognosis for these patients, providing a theoretical basis for the formulation of individual treatment plans. We firstly identified differentially expressed genes (DEGs) between HNSCC tissues and normal tissues via joint analysis based on GEO databases. Then a total of 11 hub genes were selected for single-gene prognostic analysis to identify the prognostic genes. Later, the clinical information and transcription information of HNSCC were downloaded from the TCGA database. With the application of least absolute shrinkage and selection operator (LASSO) algorithm analyses for the prognostic genes on the TCGA cohort, a prognostic model consisting of three genes (COL4A1, PLAU and ITGA5) was successfully established and the survival analyses showed that the prognostic model possessed a robust performance in the overall survival prediction. Afterward, the univariate and multivariate regression analysis indicated that the prognostic model could be an independent prognostic factor. Finally, the predicative efficiency of this model was well confirmed in an independent external HNSCC cohort.

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.


2021 ◽  
Vol 161 ◽  
pp. S509-S510
Author(s):  
S. Keek ◽  
F. Wesseling ◽  
H. Woodruff ◽  
J. van Timmeren ◽  
I. Nauta ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18512-e18512
Author(s):  
Bruna Bighetti ◽  
José Tristão Neto ◽  
Renata do Socorro Monteiro Pereira ◽  
LAÍS CRISTHINE SOUZA ◽  
Ilka Lopes Santoro ◽  
...  

e18512 Background: Cisplatin-based chemoradiotherapy (CRT) is a well-established regimen used for adjuvant and/or head-and-neck squamous cell carcinoma (HNSCC) radical treatment. The most classic protocol for chemoradiotherapy remains the administration of Cisplatin 100mg/m² EV D1 q3-week period, 3 cycles. The objective of this study is to assess the efficacy and tolerability of the weekly 40mg/m² cisplatin regimen. Methods: we conducted a retrospective study from 2007-2020 with 102 patients treated at a national reference institution. All of them with HNSCC received concurrent CRT with weekly cisplatin 40mg/m² EV D1. We analyzed the overall survival (OS), local recurrence and tolerability in this scheme. Results: The median cisplatin cumulative dose received by our patients was 240mg/m². Hence, we divided them in two groups for the analysis: Group A (41 patients) received less than 240mg/m² cisplatin total dose and Group B (61 patients) received more or equal 240mg/m² cisplatin total dose. Both groups were equally balanced between sex, clinic stage, histologic grade and clinic status. We found that the Group A experienced 5 deaths (12.2%) while the Group B experienced 6 deaths (9.8%). The mean time to recurrence disease in the Group A was 45.68 months and in Group B 60.22 months (p = 0.958). The estimated overall survival in the Group A was 150 months and in the Group B was 116.4 months (p = 0.443). Conclusions: The weekly cisplatin dose regimen showed to be feasible, more tolerable, and less toxic and with no difference in terms of OS then the classic 3-week cisplatin protocol in the CRT setting. Our group suggests that the 240mg/m² cumulative cisplatin weekly schedule should be a better option for CRT treatments then the classic cisplatin regimen. A phase III clinical trial is warranted to further understanding of this framework. Key-words: head and neck cancer, cisplatin, radiotherapy


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