Development and Validation of an Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma

Abstract

Introduction. HNSCC is the sixth most frequent type of malignant carcinoma with a low prognosis rate. In addition, autophagy is important in cancer development and progression. The purpose of this study is to investigate the potential significance of ARGs in the diagnosis and treatment of HNSCC. Materials and Methods. Expression data and clinical information of HNSCC samples were collected from the TCGA database, and a list of ARGs was obtained from the MSigDB. Then, we used R software to perform differential expression analysis and functional enrichment analysis. Further analysis was also performed to find out the survival-related ARGs in HNSCC, and two prognosis-related ARGs, FADD and NKX2-3, were selected to construct a prognosis prediction model. Moreover, some methods were applied to validate the prognosis prediction model. Finally, we used cell lines and clinical tissue samples of HNSCC to analyze the importance of FADD and NKX2-3. Results. We screened a total of 38 differentially expressed ARGs, and enrichment analysis showed that these genes were mainly involved in autophagy. Then, we selected FADD and NKX2-3 to construct a prognosis model and the risk score calculated by the model was proved to be effective in predicting the survival of HNSCC patients. Additionally, significant differences of the clinicopathological parameters could also be observed in the risk scores and the expression of NKX2-3 and FADD. The expression of FADD and NKX2-3 in cell lines and HNSCC tissue samples also showed the same trends. Conclusions. ARGs may be a potential biomarker for HNSCC prognosis, and targeted therapies for FADD and NKX2-3 are possible to be a new strategy of HNSCC treatment.

The dual role of autophagy in HPV-positive head and neck squamous cell carcinoma: a systematic review

“…Based on sequencing data of samples derived from HNSCC patients and published in “The Cancer Genome Atlas” (TCGA), numerous studies have been conducted to discover new biomarkers for HNSCC (Network 2015 ; Leemans et al 2018 ). Some of these studies (Yang et al 2020 ; Fang et al 2021 ; Guo et al 2020 ; Feng et al 2020 ; Li et al 2020 ; Ren et al 2021 ; Liu et al 2021 ; Jiang et al 2021a ; Zhang et al 2022 ) have investigated different “autophagy-related gene signatures” comprising 232 autophagy-associated genes from the Human Autophagy Database (HADb; http://autophagy.lu ) (Moussay et al 2011 ), wherein three studies included comparison of HPV + and HPV − HNSCC (Yang et al 2020 ; Fang et al 2021 ; Guo et al 2020 ). It should be noted that the majority of the genes within the prognostic gene signatures of each of those studies are not ATG genes, and that the 232 HADb gene list has not been updated since 2011.…”

New Progress in Cancer Biomarkers and Therapy

“…Next, we further investigated the eight genes used to construct the model. NK2 homeobox 3 (NKX2-3) has been reported as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) Liu et al, 2021). Suppressor APC domain containing neuroblastoma (SAPCD2) , has been reported to regulate Yap/Taz, MAPK, and mTOR signaling in various cancers, including colorectal (Luo et al, 2020) and prostate cancer (Sun et al, 2021).…”

Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma

“…Next, we further investigated the eight genes used to construct the model. NK2 homeobox 3 (NKX2-3) has been reported as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) ( Huang L. et al, 2021 ; Liu et al, 2021 ). Suppressor APC domain containing neuroblastoma (SAPCD2) ( Zhang et al, 2022 ), has been reported to regulate Yap/Taz, MAPK, and mTOR signaling in various cancers, including colorectal ( Luo et al, 2020 ) and prostate cancer ( Sun et al, 2021 ).…”