Abstract
ObjectiveTo identify biomarkers related to head and neck squamous cell carcinoma (HNSCC) metastasis and establish a prognostic model for patients with HNSCC.MethodsHNSCC mRNA expression data of metastasis and non-metastatic samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. After screening the differentially expressed genes (DEGs) in the two datasets, a prognostic model, including clinical factors and biomarkers, was established, and verified in 36 samples of HNSCC by quantitative real-time transcription (qRT)-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene sets enrichment analysis (GSEA) were consulted to explore the functions of the DEGs.ResultsIn total, 108 DEGs were identified. GSEA, GO, and KEGG analyses showed that these DEGs were mainly involved in the proliferation and metastasis of HNSCC. Six genes that were significantly related to metastasis, immune cell infiltration and prognosis were further identified to construct a prognostic gene signature. The reliability of the gene signature was verified in 36 samples of HNSCC. A prognostic model, including tumor stage, risk level, and a nomogram for prediction were further established. Receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), C-index, and calibration plots showed that the model and nomogram perform well.ConclusionWe constructed a six-gene signature and a nomogram with high performance in predicting the prognosis of patients with HNSCC metastasis.
Highlights
Head and neck cancers (HNCs) rank sixth among the most common cancers worldwide
The results showed that the metastasis group was mainly enriched in DNA replication, cell cycle, spliceosome, the P53 signaling pathway, and colorectal cancer, while the non-metastasis group was mainly enriched in arachidonic acid metabolism, the PPAR signaling pathway, and epithelial cell signaling in Helicobacter pylori infection (Figure 2A)
We found that ACTL8, BCO1, CDHR4, CEBPE, FOXA2, GNG8, METTL7B, MYO1H, SGK2, SLC13A4, SYT14, and TNFRSF13B had a significant impact on the overall survival rate (P < 0.05) (Figure 4)
Summary
Head and neck cancers (HNCs) rank sixth among the most common cancers worldwide They arise anywhere in the head and neck, including the tongue, palate, buccal mucosa, throat, and pharynx (Marur and Forastiere, 2016). According to their pathological classification, the most common type is head and neck squamous cell carcinoma (HNSCC), accounting for 95% of HNCs. Continuous exposure to tobacco or alcohol are the main risk factors for HNSCC, and HPV infection is the most important risk factor for oropharyngeal tumors (Hatcher et al, 2016; Lydiatt et al, 2017). Some biomarkers for HNSCC have been developed based on second-generation sequencing, there seems to be no perfect biomarkers that can predict the prognosis of HNSCC patients with metastasis
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