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Authors Zhang J, Hu L, Wang H, Zhi J, Hou X, Wu Y, Zheng X, Gao M
Received 16 November 2018
Accepted for publication 12 March 2019
Published 1 May 2019 Volume 2019:11 Pages 3765—3777
DOI https://doi.org/10.2147/CMAR.S194920
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Beicheng Sun
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.
Keywords: thyroid
papillary carcinoma, IDH2, function analysis, therapeutic target