Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang Province 310003, China.
Biomed Res Int. 2020 Dec 7;2020:4908427. doi: 10.1155/2020/4908427. eCollection 2020.
Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world; its pathogenic mechanism remains to be further clarified.
Robust rank aggregation (RRA) analysis was utilized to identify the metasignature dysregulated genes, which were then used for potential drug prediction. Weighted gene coexpression network analysis (WGCNA) was performed on all metasignature genes to find hub genes. DNA methylation analysis, GSEA, functional annotation, and immunocyte infiltration analysis were then performed on hub genes to investigate their potential role in HNSCC.
A total of 862 metasignature genes were identified, and 6 potential drugs were selected based on these genes. Based on the result of WGCNA, six hub genes (, , , , , and ) were selected (GS > 0.1, MM > 0.75, GS value < 0.05, and MM value < 0.05). All six genes were downregulated in tumor tissue (FDR < 0.01) and were related to the clinical stage and prognosis of HNSCC in different degrees. Methylation analysis showed that the dysregulation of , , , and may be caused by hypermethylation. Moreover, the expression level of all 6 hub genes was positively associated with immune cell infiltration, and the result of GSEA showed that all hub genes may be involved in the process of immunoregulation.
All identified hub genes could be potential biomarkers for HNSCC and provide a new insight into the diagnosis and treatment of head and neck tumors.
头颈部鳞状细胞癌(HNSCC)是世界上第六种最常见的癌症,其发病机制仍有待进一步阐明。
采用稳健秩聚合(RRA)分析鉴定失调的元特征基因,然后用于潜在药物预测。对所有元特征基因进行加权基因共表达网络分析(WGCNA),寻找枢纽基因。对枢纽基因进行 DNA 甲基化分析、GSEA、功能注释和免疫细胞浸润分析,以研究它们在 HNSCC 中的潜在作用。
共鉴定出 862 个元特征基因,并根据这些基因选择了 6 种潜在药物。基于 WGCNA 的结果,选择了 6 个枢纽基因(、、、、、)(GS > 0.1,MM > 0.75,GS 值<0.05,MM 值<0.05)。所有 6 个基因在肿瘤组织中均下调(FDR < 0.01),且与 HNSCC 的临床分期和预后呈不同程度的相关。甲基化分析表明,、、、和的失调可能是由于过度甲基化引起的。此外,所有 6 个枢纽基因的表达水平与免疫细胞浸润呈正相关,GSEA 的结果表明,所有枢纽基因可能参与免疫调节过程。
所有鉴定出的枢纽基因都可能是 HNSCC 的潜在生物标志物,为头颈部肿瘤的诊断和治疗提供了新的思路。