Identification and validation of novel prognostic signatures based on m5C methylation patterns and tumor EMT profiles in head and neck squamous cell carcinoma

作者：Guanghao Zhu, Wei Wang, Hui Yao, Haopu Li, Caiyun Zhang, Yindi Meng, Jingjie Wang, Minhui Zhu, Hongliang Zheng · 发表于：Scientific Reports · 年份：2023 · DOI：10.1038/s41598-023-45976-6 · 被引用次数：13 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Epigenetics and DNA Methylation

The role of 5-methylcytosine (m5C) in tumor initiation and progression has been increasingly recognized. However, the precise association between the regulation of m5C and the progression, metastasis, and prognosis of head and neck squamous cell carcinoma (HNSCC) has not yet been fully explored. Data from 545 HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database were analyzed. Unsupervised cluster analysis was conducted using the expression levels of m5C regulatory genes. Additionally, gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), and Cox regression analysis were utilized. Quantitative reverse transcription polymerase chain reaction (RT-qPCR), colony formation assay, transwell experiments and western blots were performed in the HNSCC cell line UM-SCC-17B to assess the expression and functional role of one of the novel signatures, CNFN. Significant expression differences were found in m5C regulatory genes between tumor and normal tissues in HNSCC. Two distinct m5C modification patterns, characterized by substantial prognostic differences, were identified. Cluster-2, which exhibited a strong association with epithelial-mesenchymal transition (EMT), was found to be associated with a poorer prognosis. Based on the m5C clusters and EMT status, differentially expressed genes (DEGs) were identified. Using DEGs, an 8-gene signature (CAMK2N1, WNT7A, F2RL1, AREG, DEFB1, CNFN, TGFBI, and CAV1) was established to develop a prognos...