Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.
Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.
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人乳腺癌细胞因子信号蛋白抑制因子的综合分析
DOI：
10.1186/s12885-021-08434-y
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发表时间：
2021-06-13
期刊：
影响因子：
3.8
通讯作者：
Rixiati Y
中科院分区：
文献类型：
--
作者：
Sun M;Tang C;Liu J;Jiang W;Yu H;Dong F;Huang C;Rixiati Y
细胞因子信号转导抑制因子（SOCS）蛋白的异常表达调节肿瘤血管生成和癌症的发展。在这项研究中，我们的目的是进行一个全面的生物信息学分析的SOCS蛋白在乳腺浸润性癌（BRCA）。BRCA患者中与SOCS家族成员相关的基因表达、甲基化水平、拷贝数、蛋白质表达和患者生存数据来自以下数据库：Oncomine、癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）、人类蛋白质图谱（HPA）、基因表达谱交互分析（GEPIA）、PCViz、cBioPortal和Kaplan-Meier RT-PCR。通过功能和途径富集分析、加权基因共表达网络分析（WGCNA）和基因集富集分析（GSEA）进行相关性分析、相互作用基因的鉴定和调控网络的构建。从TCGA数据库中提取了1109例BRCA组织和113例正常乳腺组织样本的相关数据。SOCS 2和SOCS 3在BRCA组织中的mRNA表达水平显著低于正常组织。具有高水平SOCS 3（p < 0.01）和SOCS 4（p < 0.05）mRNA的BRCA患者预计具有显著更长的总生存（OS）时间。多变量分析显示SOCS 3是OS的独立预后因素。SOCS 2（p < 0.001）、SOCS 3（p < 0.001）和SOCS 4（p < 0.01）的高mRNA表达水平以及SOCS 5（p < 0.001）的低表达水平被预测与较好的无复发生存期（RFS）显著相关。多因素分析显示SOCS 2是RFS的独立预后因素。SOCS 2和SOCS 3在临床分期越晚的肿瘤中表达越低（p < 0.05）。功能和途径富集分析以及WGCNA和GSEA显示SOCS 3及其相互作用基因显著参与JAK-STAT信号通路，表明JAK-STAT信号通路可能在BRCA血管生成和发育中起关键作用。Western blot结果显示SOCS 3过表达抑制了JAK-STAT信号通路的活性。SOCS家族蛋白在BRCA中起着非常重要的作用。SOCS 3可能是乳腺癌的一个预后因子，SOCS 2可能是一个潜在的治疗靶点。在线版本包含补充材料，可通过10.1186/s12885-021-08434-y获得。
Abnormal expression of suppressor of cytokine signaling (SOCS) proteins regulates tumor angiogenesis and development in cancers. In this study, we aimed to perform a comprehensive bioinformatic analysis of SOCS proteins in breast invasive carcinoma (BRCA). The gene expression, methylation level, copy number, protein expression and patient survival data related to SOCS family members in BRCA patients were obtained from the following databases: Oncomine, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), PCViz, cBioPortal and Kaplan-Meier plotter. Correlation analyses, identification of interacting genes and construction of regulatory networks were performed by functional and pathway enrichment analyses, weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Data related to 1109 BRCA tissues and 113 normal breast tissue samples were extracted from the TCGA database. SOCS2 and SOCS3 exhibited significantly lower mRNA expression levels in BRCA tissues than in normal tissues. BRCA patients with high mRNA levels of SOCS3 (p < 0.01) and SOCS4 (p < 0.05) were predicted to have significantly longer overall survival (OS) times. Multivariate analysis showed that SOCS3 was an independent prognostic factor for OS. High mRNA expression levels of SOCS2 (p < 0.001), SOCS3 (p < 0.001), and SOCS4 (p < 0.01), and a low expression level of SOCS5 (p < 0.001) were predicted to be significantly associated with better recurrence-free survival (RFS). Multivariate analysis showed that SOCS2 was an independent prognostic factor for RFS. Lower expression levels of SOCS2 and SOCS3 were observed in patients with tumors of more advanced clinical stage (p < 0.05). Functional and pathway enrichment analyses, together with WGCNA and GSEA, showed that SOCS3 and its interacting genes were significantly involved in the JAK-STAT signaling pathway, suggesting that JAK-STAT signaling might play a critical role in BRCA angiogenesis and development. Western blot results showed that overexpression of SOCS3 inhibited the activity of the JAK-STAT signaling pathway in vitro. SOCS family proteins play a very important role in BRCA. SOCS3 may be a prognostic factor and SOCS2 may be a potential therapeutic target in breast cancer. The online version contains supplementary material available at 10.1186/s12885-021-08434-y.
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影响因子：
5.7
作者：
Chikuma S;Kanamori M;Mise-Omata S;Yoshimura A
通讯作者：
Yoshimura A
DOI：
10.4161/jkst.24053
发表时间：
2013-07-01
期刊：
JAK-STAT
影响因子：
--
作者：
Inagaki-Ohara K;Kondo T;Ito M;Yoshimura A
通讯作者：
Yoshimura A
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1073/pnas.0601638103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Bullock, Alex N.;Debreczeni, Judit E.;Knapp, Stefan
通讯作者：
Knapp, Stefan
DOI：
10.1152/ajpheart.00570.2012
发表时间：
2013-03-01
影响因子：
4.8
作者：
Dhar, Kajari;Rakesh, Kriti;Agrawal, Devendra K.
通讯作者：
Agrawal, Devendra K.