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

 Jandee Lee  ;  Seonhyang Jeong  ;  Cho Rok Lee  ;  Cheol Ryong Ku  ;  Sang-Wook Kang  ;  Jong Ju Jeong  ;  Kee-Hyun Nam  ;  Dong Yeob Shin  ;  Woong Youn Chung  ;  Eun Jig Lee  ;  Young Suk Jo 
 MEDICINE, Vol.94(25) : 998, 2015 
Journal Title
Issue Date
Adult ; Carcinoma/metabolism* ; Carcinoma/pathology ; Carcinoma, Papillary ; Female ; Hedgehog Proteins/metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Thyroid Gland/pathology ; Thyroid Neoplasms/metabolism* ; Thyroid Neoplasms/pathology ; Transcription Factors/metabolism* ; Zinc Finger Protein GLI1
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Sang Wook(강상욱) ORCID logo https://orcid.org/0000-0001-5355-833X
Ku, Cheol Ryong(구철룡) ORCID logo https://orcid.org/0000-0001-8693-9630
Nam, Kee Hyun(남기현) ORCID logo https://orcid.org/0000-0002-6852-1190
Shin, Dong Yeob(신동엽) ORCID logo https://orcid.org/0000-0003-1048-7978
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Jan Dee(이잔디) ORCID logo https://orcid.org/0000-0003-4090-0049
Lee, Cho Rok(이초록) ORCID logo https://orcid.org/0000-0001-7848-3709
Jeong, Seonhyang(정선향) ORCID logo https://orcid.org/0000-0002-5549-9182
Chung, Woung Youn(정웅윤)
Jeong, Jong Ju(정종주) ORCID logo https://orcid.org/0000-0002-4155-6035
Jo, Young Suk(조영석) ORCID logo https://orcid.org/0000-0001-9926-8389
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