口腔鳞状细胞癌中神经周围侵犯的预后 DNA 突变和 mRNA 表达分析。

Prognostic DNA mutation and mRNA expression analysis of perineural invasion in oral squamous cell carcinoma.

机构信息

Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul, Republic of Korea.

Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.

出版信息

Sci Rep. 2024 Jan 29;14(1):2427. doi: 10.1038/s41598-024-52745-6.

DOI:10.1038/s41598-024-52745-6

PMID:38287071

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10825128/

Abstract

This study analyzed oral squamous cell carcinoma (OSCC) genomes and transcriptomes in relation to perineural invasion (PNI) and prognosis using Cancer Genome Atlas data and validated these results with GSE41613 data. Gene set enrichment analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted. We identified 22 DNA mutations associated with both overall survival (OS) and PNI. Among them, TGFBR1 and RPS6KA4 mRNAs were overexpressed, while TYRO3 and GPR137 mRNAs were underexpressed in PNI patients. Among the 141 mRNA genes associated with both OS and PNI, we found overlap with PNI-related DNA mutations, including ZNF43, TEX10, TPSD1, and PSD3. In GSE41613 data, TGFBR1, RPS6KA4, TYRO3, GPR137, TEX10 and TPSD1 mRNAs were expressed differently according to the prognosis. The 22 DNA-mutated genes clustered into nervous system development, regulation of DNA-templated transcription, and transforming growth factor beta binding. GSEA analysis of mRNAs revealed upregulation of hallmarks epithelial mesenchymal transition (EMT), TNFα signaling via NF-κB, and IL2 STAT5 signaling. EMT upregulation aligned with the TGFBR1 DNA mutation, supporting its significance in PNI. These findings suggest a potential role of PNI genes in the prognosis of OSCC, providing insights for diagnosis and treatment of OSCC.

摘要

本研究利用癌症基因组图谱数据分析了口腔鳞状细胞癌（OSCC）的基因组和转录组与神经周围侵犯（PNI）和预后的关系，并使用 GSE41613 数据验证了这些结果。进行了基因集富集分析（GSEA）、基因本体论（GO）和京都基因与基因组百科全书分析。我们确定了 22 个与总生存期（OS）和 PNI 均相关的 DNA 突变。其中，TGFBR1 和 RPS6KA4 的 mRNA 表达上调，而 TYRO3 和 GPR137 的 mRNA 表达下调与 PNI 患者有关。在与 OS 和 PNI 均相关的 141 个 mRNA 基因中，我们发现与 PNI 相关的 DNA 突变存在重叠，包括 ZNF43、TEX10、TPSD1 和 PSD3。在 GSE41613 数据中，TGFBR1、RPS6KA4、TYRO3、GPR137、TEX10 和 TPSD1 的 mRNA 根据预后表达不同。22 个 DNA 突变基因聚类为神经系统发育、DNA 模板转录调控和转化生长因子β结合。mRNA 的 GSEA 分析显示上皮间质转化（EMT）、TNFα 信号通过 NF-κB 和 IL2 STAT5 信号的特征上调。EMT 的上调与 TGFBR1 的 DNA 突变一致，支持其在 PNI 中的重要性。这些发现表明 PNI 基因在 OSCC 预后中的潜在作用，为 OSCC 的诊断和治疗提供了新的思路。