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Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma

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Abstract

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics. CA Cancer J Clin. 58:71–96, 2008.

    Article  PubMed  Google Scholar 

  2. DeLellis RA. Pathology and genetics of thyroid carcinoma. Journal of Surgical Oncology 94:662–9, 2006.

    Article  PubMed  CAS  Google Scholar 

  3. Fagin JA, Mitsiades N. Molecular pathology of thyroid cancer: diagnostic and clinical implications. Best Practice & Research Clinical Endocrinology & Metabolism 22:955–69, 2008.

    Article  CAS  Google Scholar 

  4. Barden CB, Shister KW, Zhu B, Guiter G, Greenblatt DY, Zeiger MA, Fahey TJ 3rd. Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clinical Cancer Research 9:1792–800, 2003.

    PubMed  CAS  Google Scholar 

  5. Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med.118:282–9, 1993

    PubMed  CAS  Google Scholar 

  6. Shibru D, Chung KW, Kebebew E. Recent developments in the clinical application of thyroid cancer biomarkers. Current Opinion in Oncology 20:13–8, 2008.

    Article  PubMed  CAS  Google Scholar 

  7. Kato MA, Fahey TJ 3rd. Molecular markers in thyroid cancer diagnostics. Surgical Clinics of North America 89:1139–55, 2009.

    Article  PubMed  Google Scholar 

  8. Eszlinger M, Paschke R. Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Molecular and Celular Endocrinology 322:29–37, 2010.

    Article  CAS  Google Scholar 

  9. Lee KY, Huang SM, Li S, Kim JM. Identification of differentially expressed genes in papillary thyroid cancers. Yonsei Medical Journal 50:60–7, 2009.

    Article  PubMed  CAS  Google Scholar 

  10. Liang P, Pardee AB. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967–71, 1992.

    Article  PubMed  CAS  Google Scholar 

  11. Sturtevant J. Applications of differential-display reverse transcription-PCR to molecular pathogenesis and medical mycology. Clinical Microbiology Reviews 13:408–27, 2000.

    Article  PubMed  CAS  Google Scholar 

  12. Chang KC, Komm B, Arnold NB, Korc M. The application of differential display as a gene profiling tool. Methods in Molecular Bioloy 383:31–40, 2007.

    Article  CAS  Google Scholar 

  13. http://lukemiller.org/journal/2007/08/quantifying-western-blots-without.html. Quantifying western blots without expensive commercial quantification software. (Access date: 05 October 2010)

  14. Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid 19:1351–61, 2009.

    Article  PubMed  CAS  Google Scholar 

  15. Liang P. Factors ensuring successful use of differential display. Methods 16:361–4, 1998.

    Article  PubMed  CAS  Google Scholar 

  16. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research 25:3389–402, 1997.

    Article  PubMed  CAS  Google Scholar 

  17. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S, ed. Bioinformatics Methods and Protocols: Methods in Molecular Biology. New Jersey: Humana Press, 2000; 365–386.

    Google Scholar 

  18. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I, Creech M, Gross B, Hanspers K, Isserlin R, Kelley R, Killcoyne S, Lotia S, Maere S, Morris J, Ono K, Pavlovic V, Pico AR, Vailaya A, Wang PL, Adler A, Conklin BR, Hood L, Kuiper M, Sander C, Schmulevich I, Schwikowski B, Warner GJ, Ideker T, Bader GD. Integration of biological networks and gene expression data using Cytoscape. Nature Protocols 2:2366–82, 2007.

    Article  PubMed  CAS  Google Scholar 

  19. Beaver JE, Tasan M, Gibbons FD, Tian W, Hughes TR, Roth FP. FuncBase: a resource for quantitative gene function annotation. Bioinformatics 26:1806–7, 2010.

    Article  PubMed  CAS  Google Scholar 

  20. Mostafavi S, Ray D, Warde-Farley D, Grouios C, Morris Q. GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome Biology Supplements 1 9:S4, 2008.

  21. Tye BK. MCM proteins in DNA replication. Annual Review of Biochemistry 68:649–86, 1999.

    Article  PubMed  CAS  Google Scholar 

  22. Zhu M, Wang F, Yan F, Yao PY, Du J, Gao X, Wang X, Wu Q, Ward T, Li J, Kioko S, Hu R, Xie W, Ding X, Yao X. Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization. The Journal of Biological Chemistry 283:18916–25, 2008.

    Article  PubMed  CAS  Google Scholar 

  23. Lee YS, Ha SA, Kim HJ, Shin SM, Kim HK, Kim S, Kang CS, Lee KY, Hong OK, Lee SH, Kwon HS, Cha BY, Kim JW. Minichromosome maintenance protein 3 is a candidate proliferation marker in papillary thyroid carcinoma. Experimental and Molecular Pathology 88:138–42, 2010.

    Article  PubMed  CAS  Google Scholar 

  24. Giaginis C, Vgenopoulou S, Vielh P, Theocharis S. MCM proteins as diagnostic and prognostic tumor markers in the clinical setting. Histology and Histopathology 25:351–70, 2010.

    PubMed  CAS  Google Scholar 

  25. Kebebew E, Peng M, Reiff E, Duh QY, Clark OH McMillan A. Diagnostic and prognostic value of cell-cycle regulatory genes in malignant thyroid neoplasms. World Journal of Surgery 30:767–74, 2006.

    Article  PubMed  Google Scholar 

  26. Madine MA, Swietlik M, Pelizon C, Romanowski P, Mills AD, Laskey RA The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells. Journal of Structural Biology 129:198–210, 2000.

    Article  PubMed  CAS  Google Scholar 

  27. Peter HJ, Gerber H, Studer H, Smeds S. Pathogenesis of heterogeneity in human multinodular goiter. A study on growth and function of thyroid tissue transplanted onto nude mice. The Journal of Clinical Investigation 76:1992–2002, 1985.

    Article  PubMed  CAS  Google Scholar 

  28. Salabè GB. Pathogenesis of thyroid nodules: histological classification?. Biomedicine & Pharmacotherapy 55:39–53, 2001.

    Article  Google Scholar 

  29. Thomas GA, Williams D, Williams ED. Clonal origin of thyroid tumours. In: Wynford-Thomas D, Williams ED, ed. Thyroid tumours. Edinburg: Churchill Livingstone, 1989; 38–56.

    Google Scholar 

  30. Zhang P, Zuo H, Ozaki T, Nakagomi N, Kakudo K. Cancer stem cell hypothesis in thyroid cancer. Pathology International 56:485–9, 2006.

    Article  PubMed  CAS  Google Scholar 

  31. Sertel S, Eichhorn T, Sieber S, Sauer A, Weiss J, Plinkert PK, Efferth T. Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chemico-Biological Interactions 185:42–52, 2010.

    Article  PubMed  CAS  Google Scholar 

  32. Chevillard S, Ugolin N, Vielh P, Ory K, Levalois C, Elliott D, Clayman GL, El-Naggar AK. Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications. Clinical Cancer Research 10:6586–97, 2004.

    Article  PubMed  CAS  Google Scholar 

  33. Yulug IG, See CG, Fisher EM, Ylug IG. The DAD1 protein, whose defect causes apoptotic cell death, maps to human chromosome 14. Genomics 26:433–5, 1995.

    Article  PubMed  CAS  Google Scholar 

  34. Kulke MH, Freed E, Chiang DY, Philips J, Zahrieh D, Glickman JN, Shivdasani RA. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer 47:591–603, 2008.

    Article  PubMed  CAS  Google Scholar 

  35. He H, Nagy R, Liyanarachchi S, Jiao H, Li W, Suster S, Kere J, de la Chapelle A. A susceptibility locus for papillary thyroid carcinoma on chromosome 8q24. Cancer Research 69:625–31, 2009.

    Article  PubMed  CAS  Google Scholar 

  36. Kouniavsky G, Zeiger MA. Thyroid tumorigenesis and molecular markers in thyroid cancer. Current Opinion in Oncology 22:23–9, 2010.

    Article  PubMed  CAS  Google Scholar 

  37. Yotov WV, St-Arnaud R. Mapping of the human gene for the alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to Chromosome 12q23-24.1. Mammalian Genome 7:163–4, 1996.

    Article  PubMed  CAS  Google Scholar 

  38. Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA. cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed. Biochemical and Biophysical Research Communications 253:415–22, 1998.

    Article  PubMed  CAS  Google Scholar 

  39. Woerner SM, Kloor M, Mueller A, Rueschoff J, Friedrichs N, Buettner R, Buzello M, Kienle P, Knaebel HP, Kunstmann E, Pagenstecher C, Schackert HK, Möslein G, Vogelsang H, von Knebel Doeberitz M, Gebert JF, German HNPCC Consortium. Microsatellite instability of selective target genes in HNPCC-associated colon adenomas. Oncogene 24:2525–35, 2005.

    Article  PubMed  CAS  Google Scholar 

  40. Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Modern Pathology 21(2):S37–43, 2008.

    Article  PubMed  CAS  Google Scholar 

  41. Jackson RS 2nd, Cho YJ, Liang P. TIS11D is a candidate pro-apoptotic p53 target gene. Cell Cycle 5:2889–93, 2006.

    Article  PubMed  CAS  Google Scholar 

  42. Finley DJ, Arora N, Zhu B, Gallagher L, Fahey TJ 3rd. Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. Journal of Clinical Endocrinology & Metabolism 89:3214–23, 2004.

    Article  CAS  Google Scholar 

  43. Finley DJ, Zhu B, Barden CB, Fahey TJ 3rd. Discrimination of benign and malignant thyroid nodules by molecular profiling. Annals of Surgery 240:425–36; discussion 436–7, 2004.

    Article  PubMed  Google Scholar 

  44. Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D. Regulation of p53 activity through lysine methylation. Nature 432:353–60, 2004.

    Article  PubMed  CAS  Google Scholar 

  45. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Repression of p53 activity by Smyd2-mediated methylation. Nature 444:629–32, 2006.

    Article  PubMed  CAS  Google Scholar 

  46. Komatsu S, Imoto I, Tsuda H, Kozaki KI, Muramatsu T, Shimada Y, Aiko S, Yoshizumi Y, Ichikawa D, Otsuji E, Inazawa J. Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. Carcinogenesis 30:1139–46, 2009.

    Article  PubMed  CAS  Google Scholar 

  47. Yin Y, Liu YX, Jin YJ, Hall EJ, Barrett JC. PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature 422:527–31, 2003.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by a research project (TF-09.12, 2009) from University of Gaziantep, Scientific Research Projects (BAP).

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, University of Gaziantep, 27310, Gaziantep, Turkey

    Yusuf Ziya Igci, Ahmet Arslan, Mehri Igci, Serdar Oztuzcu, Bulent Gogebakan & Ecir Ali Cakmak

  2. Department of Endocrinology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

    Ersin Akarsu

  3. Department of Pathology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

    Suna Erkilic

  4. Department of Physiology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

    Beyhan Cengiz

  5. Department of Medical Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

    A. Tuncay Demiryurek

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  1. Yusuf Ziya Igci
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Correspondence to Yusuf Ziya Igci.

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Igci, Y.Z., Arslan, A., Akarsu, E. et al. Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma. Endocr Pathol 22, 86–96 (2011). https://doi.org/10.1007/s12022-011-9157-8

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  • DOI: https://doi.org/10.1007/s12022-011-9157-8

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