IL-17 signaling pathway plays a key role in laryngeal squamous cell carcinoma with ethnic specificity

Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck squamous cell carcinoma (HNSCC) and racial disparities have been reported to exist in it. However, its molecular mechanism and associated ethnic specificity are still unclear. Here, we leveraged mRNA expression data from 2 gene expression omnibus datasets (GSE142083 & GSE117005) of Chinese samples and the cancer genome atlas (TCGA) datasets of Caucasian samples to demonstrate the expression signature of LSCC. The GSE142083 dataset was used as the discovery set since it had 53 pairs of LSCC tissues and matched adjacent normal tissues, and the GSE117005 dataset was treated as the validation set with 5 pairs of tissues. Differential gene expression analysis and enrichment pathway analysis were performed. Besides, we employed weighted gene co-expression network analysis to identify hub genes in validated pathways. The TCGA datasets were used to evaluate ethnic specificity. Immunohistochemistry (IHC) was employed to further validate the hub gene. Overall, the IL-17 signaling pathway was significantly enriched for upregulated genes in two Chinese datasets while not in TCGA datasets; and IL17RC, MAPK3, S100A8, MMP3, CXCL8, and TNFA1P3 were hub genes regulating such pathway. Therein, IL17RC might be the most important one and the IHC results displayed that the IL17RC gene upregulated in the LSCC tissue. IL-17 signaling pathway has an ethnicity-specific effect in LSCC where it is upregulated in the Chinese while not in the Caucasians and IL17RC might play a key role. Targeting genes located in the IL-17 signaling pathway may be beneficial for Chinese LSCC patients.

Automated summary

The study found significant upregulation of genes in the IL-17 signaling pathway in two Chinese datasets of Laryngeal squamous cell carcinoma (LSCC), while not in the Caucasian dataset. IL17RC was identified as a key hub gene regulating this pathway and could be a potential target for treating Chinese LSCC patients.