Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma.
Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma.
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DOI：
10.3802/jgo.2021.32.e3
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发表时间：
2021-01
影响因子：
3.9
通讯作者：
Jang HS
中科院分区：
文献类型：
--
作者：
Jung US;Min KW;Kim DH;Kwon MJ;Park H;Jang HS
AT-Rich相互作用结构域1A(ARID1A)在卵巢透明细胞癌(OCCC)中作为抑癌基因发挥着重要作用，但其临床应用尚不清楚。本研究的目的是分析ARID1a低表达患者的临床病理参数、分子相互作用和免疫渗透情况，并提供候选靶向药物。我们研究了12项合格研究中的998例口腔癌患者(采用荟萃分析)、30例口腔癌患者(来自汉阳大学古丽医院队列)和52例口腔癌患者(来自基因表达总表65986(25例)、63885(9例)和54809例(6例和12例健康人))的临床病理参数、特异性基因集/基因和免疫相关性。我们基于基因集浓缩分析(GSEA)分析了基于网络的通路，并进行了体外药物筛选。从Meta分析、Hygh队列和GEO数据来看，ARID1A的低表达与OCCC的生存不良有关。在GSEA中，ARID1a的低表达与肿瘤的侵袭过程和低免疫浸润有关。免疫组织化学检测显示CD8T细胞减少，ARID1a低表达。在通路分析中，ARID1a与血管生成内皮细胞信号转导相关。体外药物筛选显示，卡波赞替尼和比卡鲁胺能有效抑制ARID1A低表达的OCCC细胞中血管内皮生长因子A和雄激素受体等特异性HUB基因的表达。使用低ARID1A的治疗策略有助于更好地对OCCC患者进行临床管理/研究。
AT-rich interactive domain 1A (ARID1A) plays an important role as a tumor suppressor gene in ovarian clear cell carcinoma (OCCC), but the clinical application of ARID1A remains unclear. The aim of this study was to analyze clinicopathological parameters, molecular interactions and immune-infiltration in patients with low ARID1A expression and to provide candidate target drugs. We investigated the clinicopathologic parameters, specific gene sets/genes, and immunological relevance according to ARID1A expression in 998 OCCC patients from 12 eligible studies (using meta-analyses); 30 OCCC patients from the Hanyang University Guri Hospital (HYGH) cohort; and 52 OCCC patients from gene set enrichment (GSE) 65986 (25 patients), 63885 (9 patients), and 54809 (6 patients and 12 healthy people) of the Gene Expression Omnibus (GEO). We analyzed network-based pathways based on gene set enrichment analysis (GSEA) and performed in vitro drug screening. Low ARID1A expression was associated with poor survival in OCCC from the meta-analysis, HYGH cohort and GEO data. In GSEA, low ARID1A expression was related to the tumor invasion process as well as a low immune-infiltration. In silico cytometry showed that CD8 T cells were decreased with low ARID1A expression. In pathway analysis, ARID1A was associated with angiogenic endothelial cell signaling. In vitro drug screening revealed that cabozantinib and bicalutamide effectively inhibited specific hub genes, such as vascular endothelial growth factor-A and androgen receptor, in OCCC cells with low ARID1A expression. Therapeutic strategies making use of low ARID1A could contribute to better clinical management/research for patients with OCCC.
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影响因子：
4.1
作者：
Tyekucheva, Svitlana;Martin, Neil E.;Birrer, Michael
通讯作者：
Birrer, Michael
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
2.4
作者：
Choi JY;Han HH;Kim YT;Lee JH;Kim BG;Kang S;Cho NH
通讯作者：
Cho NH
DOI：
10.1093/jnci/djy088
发表时间：
2018-08-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Sauerbrei W;Taube SE;McShane LM;Cavenagh MM;Altman DG
通讯作者：
Altman DG
影响因子：
28.2
作者：
Shen J;Peng Y;Wei L;Zhang W;Yang L;Lan L;Kapoor P;Ju Z;Mo Q;Shih IeM;Uray IP;Wu X;Brown PH;Shen X;Mills GB;Peng G
通讯作者：
Peng G