Li Qiang, Jiang Sheng, Feng Tienan, Zhu Tengteng, Qian Biyun
Public Health College, Shanghai Jiao Tong University of Medicine, Shanghai, 200025, People's Republic of China.
Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
Onco Targets Ther. 2021 May 12;14:3119-3131. doi: 10.2147/OTT.S301127. eCollection 2021.
The detection rate of thyroid cancer (TC) has been continuously improved due to the development of detection technology. Epithelial-mesenchymal transition (EMT) is thought to be closely related to the malignant progression of tumors. However, the relationship between EMT-related genes (ERGs) characteristics and the diagnosis and prognosis of TC patients has not been studied.
Four datasets from Gene Expression Omnibus (GEO) were used to perform transcriptomic profile analysis. The overlapping differentially expressed ERGs (DEERGs) were analyzed using the R package "limma". Then, the hub genes, which had a higher degree, were identified by the protein-protein interaction (PPI) network. Gene expression analysis between the TC and normal data, the disease-free survival (DFS) analysis of TC patients from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort, function analysis, and immunohistochemistry (IHC) were performed to verify the importance of the hub genes. Finally, a prognostic risk scoring was constructed to predict DFS in patients with the selected genes.
A total of 43 DEERGs were identified and 10 DEERGs were considered hub ERGs, which had a high degree of connectivity in the PPI network. Then, the differential expressions of , and between TC and normal tissues were verified in the TCGA-THCA cohort and their protein expressions were also verified by IHC. DFS analysis indicated upregulations of expression (<0.01) and expression (<0.01) and downregulation of expression (=0.01) increased risks of decreased DFS for TCGA-THCA patients. Besides, by building a prognostic risk scoring model, we found that the DFS of TCGA-THCA patients was significantly worse in high-risk groups.
In summary, these hub ERGs were potential biomarkers for diagnosis and prognosis of TC, which can provide a basis for further exploring the efficacy of EMT in patients with TC.
由于检测技术的发展,甲状腺癌(TC)的检出率不断提高。上皮-间质转化(EMT)被认为与肿瘤的恶性进展密切相关。然而,EMT相关基因(ERGs)特征与TC患者的诊断和预后之间的关系尚未得到研究。
使用来自基因表达综合数据库(GEO)的四个数据集进行转录组谱分析。使用R包“limma”分析重叠的差异表达ERGs(DEERGs)。然后,通过蛋白质-蛋白质相互作用(PPI)网络鉴定具有较高度数的枢纽基因。进行TC与正常数据之间的基因表达分析、来自癌症基因组图谱甲状腺癌(TCGA-THCA)队列的TC患者的无病生存(DFS)分析、功能分析和免疫组织化学(IHC),以验证枢纽基因的重要性。最后,构建预后风险评分以预测所选基因患者的DFS。
共鉴定出43个DEERGs,其中10个DEERGs被认为是枢纽ERGs,它们在PPI网络中具有高度的连通性。然后,在TCGA-THCA队列中验证了TC与正常组织之间、和的差异表达,并且它们的蛋白质表达也通过IHC得到验证。DFS分析表明,对于TCGA-THCA患者,表达上调(<0.01)和表达上调(<0.01)以及表达下调(=0.01)会增加DFS降低的风险。此外,通过构建预后风险评分模型,我们发现高风险组中TCGA-THCA患者的DFS明显更差。
总之,这些枢纽ERGs是TC诊断和预后的潜在生物标志物,可为进一步探索EMT在TC患者中的疗效提供依据。