Functional analysis and clinical significance of the isocitrate dehydrogenase 2 gene in papillary thyroid carcinoma

Abstract

Jun Zhang,1–4 Linfei Hu,2–5 Huijuan Wang,2–5 Jingtai Zhi,2–5 Xiukun Hou,2–5 Yu Wu,6 Xiangqian Zheng,2–5 Ming Gao2–51Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 5Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 6Department of Head and Neck Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, People’s Republic of ChinaObjective: 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.Keywords: thyroid papillary carcinoma, IDH2, function analysis, therapeutic target

Keywords

• thyroid papillary carcinoma;IDH2;function analysis;therapeutic target