Functional analysis and clinical significance of the isocitrate dehydrogenase 2 gene in papillary thyroid carcinoma
Functional analysis and clinical significance of the isocitrate dehydrogenase 2 gene in papillary thyroid carcinoma
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甲状腺乳头状癌异柠檬酸脱氢酶2基因的功能分析及临床意义
DOI：
10.2147/cmar.s194920
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发表时间：
2019-05
影响因子：
3.3
通讯作者：
Gao Ming
中科院分区：
文献类型：
--
作者：
Zhang Jun;Hu Linfei;Wang Huijuan;Zhi Jingtai;Hou Xiukun;Wu Yu;Zheng Xiangqian;Gao Ming
目的：线粒体NADP+依赖性异柠檬酸脱氢酶2（IDH 2）是线粒体NADPH的主要生产者。IDH 2的相关研究主要集中在其突变机制及其临床意义上，但野生型IDH 2在肿瘤中的作用仍存在争议。已经在几种类型的癌中鉴定了改变的IDH 2水平。然而，IDH 2在甲状腺癌中的意义和表达仍然未知。研究方法：我们使用实时定量PCR（qRT-PCR）、免疫组化（IHC）染色分析和冷冻组织的western blot分析来检测IDH 2在甲状腺癌和邻近正常组织中的表达。免疫组化分析IDH 2与甲状腺癌临床病理特征的关系。随后，我们研究了野生型IDH 2在体外甲状腺癌细胞中的功能。结果如下：我们发现，IDH 2的mRNA表达和蛋白水平在肿瘤中高于在相邻组织中，当通过qRT-PCR，western blot和IHC分析进行评估时。肿瘤大小、T分期、淋巴结转移、TNM分期在IDH 2高表达组和低表达组间差异有统计学意义。多因素Logistic回归分析显示肿瘤大小和IDH 2表达与颈部淋巴结转移显著相关。此外，CCK 8水平，集落形成和侵袭细胞数量在sh-IDH 2组中减少。甲状腺癌细胞中IDH 2的上调显示出相反的效果。结论：IDH 2可能在甲状腺癌的发生发展中起重要作用。IDH 2可作为诊断和预后的潜在生物标志物，并可能成为甲状腺癌的潜在治疗靶点。
Objective: Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major producer of mitochondrial NADPH. IDH2-related research has focused on its mutation mechanism and its clinical significance, but the role of wild-type IDH2 in carcinoma remains controversial. Altered IDH2 levels have been identified in several types of carcinomas. However, the significance and expression of IDH2 in thyroid cancer remains unknown. Methods: We examined the expression of IDH2 in thyroid cancer and adjacent normal tissues using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining analyses, and western blot analysis with frozen tissues. The relationship between IDH2 and the clinicopathological features of thyroid cancer was analyzed by IHC. Subsequently, we investigated the function of wild-type IDH2 in thyroid cancer cells in vitro. Results: We found that the mRNA expression and protein levels of IDH2 were higher in tumor than in adjacent tissues, when evaluated by qRT-PCR, western blot, and IHC analyses. Tumor size, T stage, lymph node metastasis, and TNM stage showed significant differences between the IDH2 high expression and low expression groups. Multiple logistic regression analyses indicated that tumor size and IDH2 expression were significantly correlated with the occurrence of neck LNM. Furthermore, CCK8 levels, colony formation, and invasive cell number were decreased in the sh-IDH2 groups. The upregulation of IDH2 in thyroid cancer cells showed opposite effects. Conclusion: Our results indicated that IDH2 may play an important role in the development of thyroid cancer. IDH2 can be used as a potential biomarker for diagnosis and prognosis and may be a potential therapeutic target for thyroid cancer.
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DOI：
10.1126/science.1170944
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zhao S;Lin Y;Xu W;Jiang W;Zha Z;Wang P;Yu W;Li Z;Gong L;Peng Y;Ding J;Lei Q;Guan KL;Xiong Y
通讯作者：
Xiong Y
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
50.3
作者：
Xu W;Yang H;Liu Y;Yang Y;Wang P;Kim SH;Ito S;Yang C;Wang P;Xiao MT;Liu LX;Jiang WQ;Liu J;Zhang JY;Wang B;Frye S;Zhang Y;Xu YH;Lei QY;Guan KL;Zhao SM;Xiong Y
通讯作者：
Xiong Y
影响因子：
50.3
作者：
Ward PS;Patel J;Wise DR;Abdel-Wahab O;Bennett BD;Coller HA;Cross JR;Fantin VR;Hedvat CV;Perl AE;Rabinowitz JD;Carroll M;Su SM;Sharp KA;Levine RL;Thompson CB
通讯作者：
Thompson CB
影响因子：
4.6
作者：
Oh CM;Won YJ;Jung KW;Kong HJ;Cho H;Lee JK;Lee DH;Lee KH;Community of Population-Based Regional Cancer Registries
通讯作者：
Community of Population-Based Regional Cancer Registries