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GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

Authors
 Jandee Lee  ;  Seonhyang Jeong  ;  Young Suk Jo  ;  Eun Jig Lee  ;  Woong Youn Chung  ;  Dong Yeob Shin  ;  Kee-Hyun Nam  ;  Jong Ju Jeong  ;  Sang-Wook Kang  ;  Cheol Ryong Ku  ;  Cho Rok Lee 
Citation
 Medicine, Vol.94(25) : 998-998, 2015 
Journal Title
 Medicine 
ISSN
 0025-7974 
Issue Date
2015
Abstract
A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers, as well as novel therapeutic targets.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140479
DOI
10.1097/MD.0000000000000998
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
강상욱(Kang, Sang Wook) ; 구철룡(Ku, Cheol Ryong) ; 남기현(Nam, Kee Hyun) ; 신동엽(Shin, Dong Yeob) ; 이은직(Lee, Eun Jig) ; 이잔디(Lee, Jan Dee) ; 이초록(Lee, Cho Rok) ; 정웅윤(Chung, Woung Youn) ; 정종주(Jeong, Jong Ju) ; 조영석(Jo, Young Suk)
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