Identification of an immune-related signature indicating the dedifferentiation of thyroid cells.
Identification of an immune-related signature indicating the dedifferentiation of thyroid cells.
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DOI：
10.1186/s12935-021-01939-3
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发表时间：
2021-04-23
影响因子：
5.8
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Wang X;Peng W;Li C;Qin R;Zhong Z;Sun C
在间变性甲状腺癌（ATC）中，免疫细胞在肿瘤微环境中占比很大。然而，ATC中免疫相关基因（IRG）的表达模式尚不清楚。我们的研究旨在确定一种能指示甲状腺细胞去分化的免疫相关特征。
我们在基因表达综合数据库（Gene Expression Omnibus database）中比较了ATC与甲状腺乳头状癌（PTC）或正常甲状腺组织之间在甲状腺分化评分（TDS）、免疫细胞浸润及富集通路方面的差异。在癌症基因组图谱数据库（The Cancer Genome Atlas database）中，采用单变量和多变量Cox分析筛选与预后相关的IRG。构建风险评分后，我们通过应用受试者工作特征曲线和 Kaplan - Meier曲线，研究其对分化和生存的预测价值。我们进一步探究了该风险评分与重要免疫检查点分子、浸润免疫细胞及免疫治疗反应之间的关联。
与PTC或正常甲状腺组织相比，ATC表现出较低的TDS值，以及免疫细胞更高程度的富集和炎症反应的激活。定量分析和免疫组化染色证实，与正常甲状腺样本和PTC相比，大多数ATC细胞系和ATC组织中MMP9表达较高，而SDC2表达较低。较高的风险评分表明去分化程度更高且预后更差。此外，风险评分与免疫检查点分子PDL1、CTLA4、IDO1和HAVCR2以及多种免疫细胞的浸润呈正相关。重要的是，我们发现风险评分较高的样本相比评分较低的样本，对免疫治疗往往有更好的反应。
我们的研究结果表明，风险评分不仅有助于判断甲状腺癌的分化程度和预后，还有助于预测免疫细胞浸润情况和免疫治疗反应。
在线版本包含补充材料，网址为10.1186/s12935 - 021 - 01939 - 3。
Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells. We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy. Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores. Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response. The online version contains supplementary material available at 10.1186/s12935-021-01939-3.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
5.2
作者：
Lin, Peng;Guo, Yi-nan;Chen, Gang
通讯作者：
Chen, Gang
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H
DOI：
10.1016/j.jsbmb.2019.105390
发表时间：
2019-09-01
影响因子：
4.1
作者：
Bauriaud-Mallet, Mathilde;Vija-Racaru, Lavinia;Silvente-Poirot, Sandrine
通讯作者：
Silvente-Poirot, Sandrine
影响因子：
28.4
作者：
Maniakas, Anastasios;Dadu, Ramona;Zafereo, Mark
通讯作者：
Zafereo, Mark