Identification of tumor microenvironment-related genes in lower-grade gliomas by mining TCGA database.
Identification of tumor microenvironment-related genes in lower-grade gliomas by mining TCGA database.
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通过挖掘TCGA数据库鉴定下级神经胶质瘤中肿瘤微环境相关的基因。
DOI：
10.21037/tcr-20-1079
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发表时间：
2020-08
影响因子：
0.9
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Liang H;Huang C
低级别胶质瘤（LGGs）是脑肿瘤中普遍存在的致命分支。寻找与诊断和治疗相关的生物标志物对LGG的治疗至关重要。通过从TCGA数据库中挖掘mRNA表达谱，有可能揭示LGG中肿瘤微环境与总生存期（OS）之间的潜在联系。我们的主要目的是探索在LGG微环境中可用于诊断或治疗的关键基因。基于ESTIMATE算法，分别计算免疫和基质评分以测量免疫细胞和基质细胞的浸润程度。根据免疫评分和基质评分将TCGA数据库中的LGG样本分为高分组和低分组，并通过比较两组中基因表达水平来选择差异表达基因（DEG）。功能富集分析和蛋白质-蛋白质相互作用（PPI）网络进行分析DEG。最后，使用来自CGGA数据集的另一个独立的LGG队列对选定的DEG进行验证。结果表明，免疫/基质评分与LGG预后相关。此外，对每种亚型进行的生存分析显示，免疫/基质评分仅与星形细胞瘤、IDH野生型的预后显著相关，在其他亚型中没有显著的统计学差异。功能富集分析和蛋白质-蛋白质相互作用（PPI）网络进一步表明，上调的DEG主要参与免疫应答、质膜和细胞因子结合。因此，获得了一系列对预后具有显著影响并且与肿瘤微环境显著相关的基因。基于ESTIMATE算法，我们首先探索了不同LGG亚型的免疫/基质评分与预后之间的关系，结果显示，评分仅与星形细胞瘤、IDH-野生型的预后密切相关。进一步对星形细胞瘤、IDH-野生型患者的基因表达谱进行了全面的生物信息学分析，确定CASP 8、TRIM 6、TRIM 38、PARP 9、NMI、EPSTI 1、DTX 3L和AGBL 2为肿瘤微环境相关基因，可能参与LGG的发生、发展和侵袭。
Lower-grade gliomas (LGGs) are ubiquitous and fatal branches of brain neoplasm. Finding biomarkers related to diagnosis and treatment is essential for the treatment of LGG. It is possible to reveal the potential links between tumor microenvironment and overall survival (OS) in LGG by mining the mRNA expression profile from the TCGA database. Our primary purpose was to explore key genes that can be applied for diagnosis or treatment in LGG microenvironment. Based on the ESTIMATE algorithm, the immune and stromal scores were calculated to measure the extent of infiltration of immune cells and stromal cells, respectively. The LGG samples from TCGA database were assigned into high- or low-score groups per the immune and stromal scores and differentially expressed genes (DEGs) were selected by comparing gene expression levels in the two groups. Functional enrichment analysis and protein-protein interaction (PPI) networks were performed to analyze DEGs. Finally, selected DEGs were validated using another independent LGG cohort from CGGA dataset. The results indicated that immune/stromal scores correlated with LGG prognosis. Furtherly, survival analysis conducted for each subtype shown that immune/stromal scores were only significantly associated with the prognosis of astrocytoma, IDH-wildtype, and there was no significant statistical difference in the other subtypes. Functional enrichment analysis and protein-protein interaction (PPI) networks further showed that the upregulated DEGs were primarily involved in immune response, plasma membrane, and cytokine binding. Accordingly, a series of genes that have significant impacts on prognosis and are significantly associated with the tumor microenvironment were obtained. Based on the ESTIMATE algorithm, we first explored the relationship between immune/stromal scores and prognosis in different subtypes of LGG and the result shown that the scores were only strongly associated with the prognosis of astrocytoma, IDH-wildtype. Furtherly, a comprehensive bioinformatics analysis of the gene expression profiles of astrocytoma, IDH-wildtype patients was conducted, CASP8, TRIM6, TRIM38, PARP9, NMI, EPSTI1, DTX3L and AGBL2 were identified as tumor microenvironment-related genes, may be involved in the occurrence, development, and invasion of LGG.
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影响因子：
20.3
作者：
Aguiar, RCT;Yakushijin, Y;Shipp, MA
通讯作者：
Shipp, MA
影响因子：
15.9
作者：
Silver, Daniel J.;Sinyuk, Maksim;Lathia, Justin D.
通讯作者：
Lathia, Justin D.
靶向 p21 激活激酶 1 通过 Raf1/MEK1/ERK 信号传导抑制食管鳞状细胞癌细胞的生长和转移
影响因子：
8.4
作者：
Chen, Liang;Bi, Shuning;Xie, Songqiang
通讯作者：
Xie, Songqiang
影响因子：
32.4
作者：
Stark GR;Darnell JE Jr
通讯作者：
Darnell JE Jr
DOI：
10.1056/nejmoa1402121
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Brat DJ;Verhaak RG;Aldape KD;Yung WK;Salama SR;Cooper LA;Rheinbay E;Miller CR;Vitucci M;Morozova O;Robertson AG;Noushmehr H;Laird PW;Cherniack AD;Akbani R;Huse JT;Ciriello G;Poisson LM;Barnholtz-Sloan JS;Berger MS;Brennan C;Colen RR;Colman H;Flanders AE;Giannini C;Grifford M;Iavarone A;Jain R;Joseph I;Kim J;Kasaian K;Mikkelsen T;Murray BA;O'Neill BP;Pachter L;Parsons DW;Sougnez C;Sulman EP;Vandenberg SR;Van Meir EG;von Deimling A;Zhang H;Crain D;Lau K;Mallery D;Morris S;Paulauskis J;Penny R;Shelton T;Sherman M;Yena P;Black A;Bowen J;Dicostanzo K;Gastier-Foster J;Leraas KM;Lichtenberg TM;Pierson CR;Ramirez NC;Taylor C;Weaver S;Wise L;Zmuda E;Davidsen T;Demchok JA;Eley G;Ferguson ML;Hutter CM;Mills Shaw KR;Ozenberger BA;Sheth M;Sofia HJ;Tarnuzzer R;Wang Z;Yang L;Zenklusen JC;Ayala B;Baboud J;Chudamani S;Jensen MA;Liu J;Pihl T;Raman R;Wan Y;Wu Y;Ally A;Auman JT;Balasundaram M;Balu S;Baylin SB;Beroukhim R;Bootwalla MS;Bowlby R;Bristow CA;Brooks D;Butterfield Y;Carlsen R;Carter S;Chin L;Chu A;Chuah E;Cibulskis K;Clarke A;Coetzee SG;Dhalla N;Fennell T;Fisher S;Gabriel S;Getz G;Gibbs R;Guin R;Hadjipanayis A;Hayes DN;Hinoue T;Hoadley K;Holt RA;Hoyle AP;Jefferys SR;Jones S;Jones CD;Kucherlapati R;Lai PH;Lander E;Lee S;Lichtenstein L;Ma Y;Maglinte DT;Mahadeshwar HS;Marra MA;Mayo M;Meng S;Meyerson ML;Mieczkowski PA;Moore RA;Mose LE;Mungall AJ;Pantazi A;Parfenov M;Park PJ;Parker JS;Perou CM;Protopopov A;Ren X;Roach J;Sabedot TS;Schein J;Schumacher SE;Seidman JG;Seth S;Shen H;Simons JV;Sipahimalani P;Soloway MG;Song X;Sun H;Tabak B;Tam A;Tan D;Tang J;Thiessen N;Triche T Jr;Van Den Berg DJ;Veluvolu U;Waring S;Weisenberger DJ;Wilkerson MD;Wong T;Wu J;Xi L;Xu AW;Yang L;Zack TI;Zhang J;Aksoy BA;Arachchi H;Benz C;Bernard B;Carlin D;Cho J;DiCara D;Frazer S;Fuller GN;Gao J;Gehlenborg N;Haussler D;Heiman DI;Iype L;Jacobsen A;Ju Z;Katzman S;Kim H;Knijnenburg T;Kreisberg RB;Lawrence MS;Lee W;Leinonen K;Lin P;Ling S;Liu W;Liu Y;Liu Y;Lu Y;Mills G;Ng S;Noble MS;Paull E;Rao A;Reynolds S;Saksena G;Sanborn Z;Sander C;Schultz N;Senbabaoglu Y;Shen R;Shmulevich I;Sinha R;Stuart J;Sumer SO;Sun Y;Tasman N;Taylor BS;Voet D;Weinhold N;Weinstein JN;Yang D;Yoshihara K;Zheng S;Zhang W;Zou L;Abel T;Sadeghi S;Cohen ML;Eschbacher J;Hattab EM;Raghunathan A;Schniederjan MJ;Aziz D;Barnett G;Barrett W;Bigner DD;Boice L;Brewer C;Calatozzolo C;Campos B;Carlotti CG Jr;Chan TA;Cuppini L;Curley E;Cuzzubbo S;Devine K;DiMeco F;Duell R;Elder JB;Fehrenbach A;Finocchiaro G;Friedman W;Fulop J;Gardner J;Hermes B;Herold-Mende C;Jungk C;Kendler A;Lehman NL;Lipp E;Liu O;Mandt R;McGraw M;Mclendon R;McPherson C;Neder L;Nguyen P;Noss A;Nunziata R;Ostrom QT;Palmer C;Perin A;Pollo B;Potapov A;Potapova O;Rathmell WK;Rotin D;Scarpace L;Schilero C;Senecal K;Shimmel K;Shurkhay V;Sifri S;Singh R;Sloan AE;Smolenski K;Staugaitis SM;Steele R;Thorne L;Tirapelli DP;Unterberg A;Vallurupalli M;Wang Y;Warnick R;Williams F;Wolinsky Y;Bell S;Rosenberg M;Stewart C;Huang F;Grimsby JL;Radenbaugh AJ;Zhang J
通讯作者：
Zhang J