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通过生物信息学分析鉴定和验证参与甲状腺乳头状癌发生发展的核心基因

Identification and Validation of Core Genes Involved in the Development of Papillary Thyroid Carcinoma via Bioinformatics Analysis.

作者信息

Li Xiaoyan, He Jing, Zhou Mingxia, Cao Yun, Jin Yiting, Zou Qiang

机构信息

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Int J Genomics. 2019 Sep 8;2019:5894926. doi: 10.1155/2019/5894926. eCollection 2019.

Abstract

BACKGROUND

Papillary thyroid carcinoma (PTC) is a common endocrine malignant neoplasm, and its incidence increases continuously worldwide in the recent years. However, efficient clinical biomarkers were still deficient; the present research is aimed at exploring significant core genes of PTC.

METHODS

We integrated three cohorts to identify hub genes and pathways associated with PTC by comprehensive bioinformatics analysis. Expression profiles GSE33630, GSE35570, and GSE60542, including 114 PTC tissues and 126 normal tissues, were enrolled in this research. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to search for the crucial biological behaviors and pathways involved in PTC carcinogenesis. Protein-protein interaction (PPI) network was constructed, and significant modules were deeply studied.

RESULTS

A total of 831 differentially expressed genes (DEGs) were discovered, comprising 410 upregulated and 421 downregulated genes in PTC tissues compared to normal thyroid tissues. PPI network analysis demonstrated the interactions between those DEGs, and top 10 pivotal genes (, , , , , , , , , and ) with highest degree of connectivity were extracted from the network and verified by TCGA dataset and RT-PCR experiment of PTC samples. Four of the hub genes (, , , and ) were linked to the prognosis of PTC patients and considered as clinically relevant core genes via survival analysis.

CONCLUSION

In conclusion, we propose a series of key genes associated with PTC development and these genes could serve as the diagnostic biomarkers or therapeutic targets in the future treatment for PTC.

摘要

背景

甲状腺乳头状癌(PTC)是一种常见的内分泌恶性肿瘤,近年来其在全球的发病率持续上升。然而,有效的临床生物标志物仍然匮乏;本研究旨在探索PTC的重要核心基因。

方法

我们整合了三个队列,通过综合生物信息学分析来识别与PTC相关的枢纽基因和通路。本研究纳入了表达谱GSE33630、GSE35570和GSE60542,包括114例PTC组织和126例正常组织。利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析来寻找PTC致癌过程中涉及的关键生物学行为和通路。构建蛋白质-蛋白质相互作用(PPI)网络,并对重要模块进行深入研究。

结果

共发现831个差异表达基因(DEG),与正常甲状腺组织相比,PTC组织中有410个上调基因和421个下调基因。PPI网络分析展示了这些DEG之间的相互作用,从网络中提取了连接度最高的前10个关键基因(,,,,,,,,,和),并通过TCGA数据集和PTC样本的RT-PCR实验进行了验证。通过生存分析,其中4个枢纽基因(,,,和)与PTC患者的预后相关,并被视为临床相关核心基因。

结论

总之,我们提出了一系列与PTC发展相关的关键基因,这些基因可作为未来PTC治疗中的诊断生物标志物或治疗靶点。

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