title: Overexpression of HIF-1α, metallothionein and SLUG is associated with high TNM stage and lymph node metastasis in papillary thyroid carcinoma.
abstract: Hypoxia inducible factor-1α (HIF-1α) is upregulated by hypoxia, and involved in tumor growth and metastasis in many malignant tumors including papillary thyroid carcinoma (PTC). Metallothionein (MT) is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. SLUG is a member of SNAIL superfamily of zinc finger transcriptional factors implicated in epithelial-mesenchymal transition (EMT). The purpose of this study was to examine HIF-1α, MT and SLUG expression in PTC and assess association of their expression with clinicopathological indicators. HIF-1α, MT and SLUG protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of HIF-1α, MT and SLUG was significantly correlated with high TNM stage (P=0.003, 0.002, 0.024, respectively) and lymph node metastasis (LNM) (P<0.001 for all three molecules). Furthermore, HIF-1α, MT and SLUG protein expression were correlated with one another. Concomitant high expression of any two of these three molecules had stronger correlation with high TNM stage (P≤0.001 for HIF-1α/MT, MT/SLUG and HIF-1α/SLUG) and LNM (P=0.008, 0.002, 0.019 for HIF-1α/MT, MT/SLUG and HIF-1α/SLUG, respectively) than did each alone, and concomitant high expression of all these three molecules is significantly associated with high TNM stage and LNM as compared with cases not showing such expression (P<0.001). These results demonstrated that the evaluation of HIF-1α, MT and SLUG expression in PTC may be useful in predicting the risk of LNM and high TNM stage.
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Chao-Ran
authors.initials: CR
authors.lastname: Dong
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Qi-Feng
authors.initials: QF
authors.lastname: Jiang
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital Shatin, N.T., Hong Kong, China.
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D000071250:Snail Family Transcription Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D008668:Metallothionein
keywords: Hypoxia inducible factor-1α; SLUG; metallothionein; papillary thyroid carcinoma