AUTHOR=Yin Ji , He Xinling , Xia Hui , He Lu , Li Daiying , Hu Lanxin , Zheng Sihan , Huang Yanlin , Li Sen , Hu Wenjian 

TITLE=Head and Neck Squamous Cell Carcinoma Subtypes Based on Immunologic and Hallmark Gene Sets in Tumor and Non-tumor Tissues

JOURNAL=Frontiers in Surgery

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2022.821600

DOI=10.3389/fsurg.2022.821600

ISSN=2296-875X

ABSTRACT=Non-tumour tissue has a significant impact on the prognosis of head and neck squamous cell carcinoma (HNSCC). Previous studies for HNSCC have mainly focused on tumour tissue, greatly neglecting the role of non-tumour tissue. This study aimed to identify HNSCC subtypes and prognostic gene sets based on activity changes of immunologic and hallmark gene sets in tumour and adjacent non-tumour tissues to improve patient prognosis. In the study, we used gene set variation analysis (GSVA) to estimate the relative enrichment of gene sets over the sample population, and identified relevant subtypes of HNSCC by Cox regression analysis and the non-negative matrix factorization (NMF) method. The representative gene sets were identified by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen out potential prognostic gene sets and establish a risk model. Finally, genes encompassed in each prognostic gene set were obtained and subjected to enrichment analysis and protein–protein interaction (PPI) in tumour and non-tumour tissues.  We identified three subtypes of HNSCC based on gene sets in tumour and non-tumour tissues, and patients with subtype 1 had a higher survival rate than subtypes 2 and 3. The subtypes were related to the survival status, pathological stage, and T stage of HNSCC patients. 450 differentially gene sets and 39 representative gene sets were obtained by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The prognostic model was constructed by LASSO regression analysis, including five prognostic gene sets. Kaplan-Meier analysis indicated that different risk groups and the five prognostic gene sets were associated with survival status in the model. Finally, enrichment analysis and PPI indicated that non-tumour and tumour tissues affect the prognosis of HNSCC patients in different ways.