Identification of a new anoikis-related gene signature for prognostic significance in head and neck squamous carcinomas

Abstract

Anoikis, a mode of programmed cell death, is essential for normal development and homeostasis in the organism and plays an important role in the onset and progression of cancers. The authors of this research sought to establish a gene signature associated with anoikis to predict therapy outcomes and patient prognosis for individuals with head and neck squamous cell carcinoma (HNSCC). Transcriptome data of anoikis-related genes (ARGs) in individuals with HNSCC were retrieved from public databases to aid in the formulation of the gene signature. A novel ARG signature was then created using a combination of the Least Absolute Shrinkage and Selection Operator regression and Cox regression analysis. The relationship between ARGs and tumor immune microenvironment in HNSCC was explored using single-cell analysis. HNSCC individuals were classified into high-risk and low-risk groups as per the median value of risk score. The study also investigated the variations in the infiltration status of immune cells, tumor microenvironment, sensitivity to immunotherapy and chemotherapeutics, as well as functional enrichment between the low-risk and high-risk categories. A total of 18 ARGs were incorporated in the formulation of the signature. Our signature’s validity as a standalone predictive predictor was validated by multivariate Cox regression analysis and Kaplan–Meier survival analysis. Generally, the prognosis was worse for high-risk individuals. Subjects in the low-risk groups had a better prognosis and responded in a better way to combination immunotherapy, had higher immunological ratings and activity levels, and had more immune cell infiltration. In addition, gene set enrichment analysis findings showed that the low-risk subjects exhibited heightened activity in several immune-related pathways. However, the high-risk patients responded better to chemotherapy. The aim of this research was to develop a new ARG signature to predict the prognosis and sensitivity to immunotherapeutic and chemotherapeutic schemes for HNSCC patient. As a result, this could help spur the creation of new chemotherapeutics and immunotherapeutic approaches for patients with HNSCC.