Laboratory Animal Center, Shanxi Medical University, Taiyuan, China.
Taiyuan Zoo, Taiyuan, China.
Mol Carcinog. 2020 Nov;59(11):1302-1316. doi: 10.1002/mc.23258.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. However, the molecular mechanism underlying its development and progression is yet unclear. Genes that are differentially expressed, that is, differentially expressed genes (DEGs), between normal and diseased tissues are believed to be involved in disease development and progression. To identify the DEGs in OSCC and explore their role in occurrence and progression, we established a Chinese hamster OSCC model, determined the DEG, screened the identified DEGs, and performed Gene Ontology (GO) and KEGG enrichment analyses. A protein-protein interaction (PPI) network was generated to screen potential candidate genes. We then analyzed the expression, tumor stage and prognosis of candidate genes using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, we verified the candidate DEGs by quantitative real-time PCR and Gene Expression Omnibus analysis. The results showed 194 significantly DEGs, 140 enriched GO terms, and 8 KEGG pathways, which suggested that OSCC was closely related to the immune system, cell migration, and extracellular matrix. GEPIA and PPI network analysis revealed that SPP1, TNC, and ACTA1 were significantly related to tumor staging; SPP1, tissue inhibitors of matrix metallopeptidases (MMPs) 1 (TIMP1), and ACTA1 were closely related to prognosis. The scores for the top five highest degree genes were close, and the TIMP1/MMP9 axis appeared to be at the center of the PPI network, indicating that expression changes in the TIMP1/MMP9 axis and related genes may be involved in tumor invasion and metastasis. These findings provide novel insights into the mechanism of oral cancer.
口腔鳞状细胞癌（OSCC）是头颈部常见的恶性肿瘤。然而，其发生和发展的分子机制尚不清楚。正常组织和病变组织之间差异表达的基因，即差异表达基因（DEGs），被认为参与了疾病的发生和发展。为了鉴定 OSCC 中的 DEGs，并探讨其在发生和进展中的作用，我们建立了中国仓鼠 OSCC 模型，确定了 DEG，筛选出已鉴定的 DEG，并进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。生成了蛋白质-蛋白质相互作用（PPI）网络以筛选潜在的候选基因。然后，我们使用基因表达谱分析交互分析（GEPIA）数据库分析候选基因的表达、肿瘤分期和预后。最后，我们通过定量实时 PCR 和基因表达综合分析（GEO）数据库验证了候选 DEG。结果显示 194 个显著差异表达基因（DEGs），140 个富集的 GO 术语和 8 个 KEGG 通路，这表明 OSCC 与免疫系统、细胞迁移和细胞外基质密切相关。GEPIA 和 PPI 网络分析表明 SPP1、TNC 和 ACTA1 与肿瘤分期显著相关；SPP1、基质金属蛋白酶组织抑制剂 1（TIMP1）和 ACTA1 与预后密切相关。前五个最高度基因的分数接近，TIMP1/MMP9 轴似乎处于 PPI 网络的中心，表明 TIMP1/MMP9 轴和相关基因的表达变化可能参与了肿瘤的侵袭和转移。这些发现为口腔癌的发病机制提供了新的见解。
