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对现有微阵列数据的二次分析揭示了皮肤鳞状细胞癌的潜在基因驱动因素。

Secondary analysis of existing microarray data reveals potential gene drivers of cutaneous squamous cell carcinoma.

作者信息

Liu Haibo, Chen Daxiang, Liu Ping, Xu Shuqia, Lin Xunxun, Zeng Ruixi

机构信息

Division of Plastic and Reconstructive Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Department of Laboratory Medicine, Dermatology Hospital, Southern Medical University, Guangzhou, China.

出版信息

J Cell Physiol. 2019 Sep;234(9):15270-15278. doi: 10.1002/jcp.28172. Epub 2019 Jan 29.

Abstract

Cutaneous squamous-cell carcinoma (cSCC) is the second most common skin cancer, with an increasing incidence in recent years. To define the molecular basis that drive cSCC development and progression, this study aimed at identifying potential novel molecular targets for the diagnosis and therapy of patients with cSCC. Two data sets with the accession number GSE45164 and GSE66359 were downloaded from Gene Expression Omnibus (GEO) database. After the identification of differentially expressed genes (DEGs) from these two data sets, respectively, between cSCC samples and controls, a combination of DEGs from these two data sets were subjected to the following analyses, including functional annotation, protein-protein interaction (PPI) network and module construction, transcription factor (TF)-target regulation prediction, and drug-gene interaction predictive analysis. A total of 204 upregulated genes and 213 downregulated genes were found in two data sets which were used for the follow-up analysis. Upregulated and downregulated genes were mainly involved in the functions such as cell division, mitotic nuclear division, cell cycle, and p53 signaling pathway. Interferon induced protein family members and proteasome subunit members were involved in the TF-target regulatory network, such as PSMB8, CXCL10, and IFIT3. Eight upregulated genes ( TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15) that were hub genes in the PPI network and significant modules were identified in the predicted drug-gene interaction. In conclusion, TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15 may be potential targets for the diagnosis and therapy of patients with cSCC.

摘要

皮肤鳞状细胞癌(cSCC)是第二常见的皮肤癌,近年来发病率不断上升。为了确定驱动cSCC发生和发展的分子基础,本研究旨在识别cSCC患者诊断和治疗的潜在新分子靶点。从基因表达综合数据库(GEO)下载了登录号为GSE45164和GSE66359的两个数据集。分别从这两个数据集中鉴定出cSCC样本与对照之间的差异表达基因(DEG)后,将这两个数据集的DEG组合进行以下分析,包括功能注释、蛋白质-蛋白质相互作用(PPI)网络和模块构建、转录因子(TF)-靶标调控预测以及药物-基因相互作用预测分析。在两个数据集中共发现204个上调基因和213个下调基因,用于后续分析。上调和下调基因主要参与细胞分裂、有丝分裂核分裂、细胞周期和p53信号通路等功能。干扰素诱导蛋白家族成员和蛋白酶体亚基成员参与了TF-靶标调控网络,如PSMB8、CXCL10和IFIT3。在预测的药物-基因相互作用中,鉴定出8个上调基因(TOP2A、CXCL8、RRM2、PSMB8、PSMB9、PBK、CXCL10和ISG15)是PPI网络和重要模块中的枢纽基因。总之,TOP2A、CXCL8、RRM2、PSMB8、PSMB9、PBK、CXCL10和ISG15可能是cSCC患者诊断和治疗的潜在靶点。

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