title: Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma.
abstract: Some studies showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our previous limited data specifically suggested a possible pathogenic role of CCDC67 in papillary thyroid cancer (PTC), but this has not been firmly established. The present study was to further investigate and establish this role of CCDC67 in PTC.
  
  
  
  The expression of CCDC67, both at mRNA and protein levels, was sharply down-regulated in PTC compared with normal thyroid tissues. Lower CCDC67 expression was significantly associated with aggressive tumor behaviors, such as advanced tumor stages and lymph node metastasis, as well as BRAF mutation. Introduced expression of CCDC67 in TPC-1 cells robustly inhibited cell proliferation, colony formation and migration, induced G1 phase cell cycle arrest, and increased cell apoptosis.
  
  
  
  Primary PTC tumors and matched normal thyroid tissues were obtained from 200 unselected patients at the initial surgery for detection of CCDC67 mRNA and protein by RT-PCR and Western blotting analyses, respectively. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. Clinicopathological data were retrospectively reviewed for correlation analyses. PTC cell line TPC-1 with stable transfection of CCDC67 was used to investigate the functions of CCDC67.
  
  
  
  This large study demonstrates down-regulation of CCDC67 in PTC, an inverse relationship between CCDC67 expression and PTC aggressiveness and BRAF mutation, and a robust inhibitory effect of CCDC67 on PTC cellular activities. These results are consistent with CCDC67 being a novel and impaired tumor suppressor gene in PTC, providing important prognostic and therapeutic implications for this cancer.
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: De Tao
authors.initials: DT
authors.lastname: Yin
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.|Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Endocrinology and Metabolism, the Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C576056:DEUP1 protein, human; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: CCDC67; molecular pathogenesis; prognostic marker; thyroid cancer; tumor suppressor