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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent type of malignant carcinoma with a low prognosis rate
232 autophagy-related genes (ARGs) derived from Molecular Signatures Database (MSigDB) were included in our study and there were 38 differentially expressed ARGs, including 28 upregulated (APOL1, BIRC5, VMP1, FADD, ITGB4, ITGA6, EIF4EBP1, TNFSF10, TP63, HIF1A, EGFR, ITGA3, BAK1, CTSL, CDKN2A, IL24, NGR1, SERPINA1, CXCR4, SPHK1, VEGFA, BID, EIF2AK2, RGS19, IFNG, DDIT3, SPNS1, and IRGM) and 10 downregulated ARGs (FOS, CCL2, HSPB8, PTK6, TP53INP2, NRG3, NKX2-3, NRG2, MAP1LC3C, and PRKN), with thresholds of ∣log 2 fold change ðFCÞ ∣ >2
We applied it for visualizing the expression level of the differentially expressed ARGs between HNSCC tissues and nontumor tissues (Figure 1(c))
Summary
HNSCC is the sixth most frequent type of malignant carcinoma with a low prognosis rate. Further analysis was performed to find out the survivalrelated ARGs in HNSCC, and two prognosis-related ARGs, FADD and NKX2-3, were selected to construct a prognosis prediction model. We used cell lines and clinical tissue samples of HNSCC to analyze the importance of FADD and NKX2-3. 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. Significant differences of the clinicopathological parameters could 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 showed the same trends. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy of the world. It is significant to develop new therapeutic strategies, so that we could treat tumors with much more precision
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