Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas

Paricharttanakul,N.  Monique; Saharat,Kittirat; Chokchaichamnankit,Daranee; Punyarit,Phaibul; Srisomsap,Chantragan; Svasti,Jisnuson

doi:10.3892/or.2016.4567

Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas

Authors:
- N. Monique Paricharttanakul
- Kittirat Saharat
- Daranee Chokchaichamnankit
- Phaibul Punyarit
- Chantragan Srisomsap
- Jisnuson Svasti
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Affiliations: Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand, Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, Thailand, Department of Clinical Pathology, Army Institute of Pathology, Phramongkutklao Medical Center, Bangkok, Thailand
Published online on: January 15, 2016 https://doi.org/10.3892/or.2016.4567
Pages: 2286-2296

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Abstract

Thyroid cancer is the most common human endocrine malignancy with increasing global incidence. Papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC) are well-differentiated thyroid cancers (WDTC) accounting for 95% of all thyroid cancer cases, with survival rates of almost 100% when diagnosed early. Since PTC and FTC have different modes of metastasis, they require different treatment strategies. Standard diagnosis by fine needle aspiration with cytopathological examination can be inaccurate in approximately 10-30% of all cases and difficult to definitively classify as WDTC. Currently, there is no single or panel of biomarkers available for thyroid cancer diagnosis and classification. This study identified novel biomarkers for thyroid cancer diagnosis and classification using proteomics, which may be translated into a biomarker panel for clinical application. Two-dimensional SDS-PAGE and mass spectrometry were used to identify potential biomarkers in papillary and follicular thyroid carcinoma cell lines, and the biomarkers were validated in five PTC and five FTC tissues, with their adjacent normal tissues from Thai patients. Eight biomarkers could distinguish PTC from normal tissues, namely enolase 1, triose phosphate isomerase, cathepsin D, annexin A2, cofilin 1, proliferating cell nuclear antigen (PCNA), copine 1 and heat shock protein 27 kDa (HSP27). These biomarkers can also discriminate FTC from normal tissues, except for annexin A2. On the contrary, annexin A2, cofilin 1, PCNA and HSP27 can be used to classify the types of WDTC. These findings have potential for use as a novel multi-marker panel for more accurate diagnosis and classification to better guide physicians on thyroid cancer treatment. Moreover, our results suggest the involvement of proteins in cell growth and proliferation, and the p53 pathway in the carcinogenesis of WDTC, which may lead to targeted therapy for thyroid cancer.

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1	International Agency for Research on Cance: GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. World Health Organization. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed Sept 2, 2014.
2	Pellegriti G, Frasca F, Regalbuto C, Squatrito S and Vigneri R: Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013:9652122013. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
4	Kondo T, Ezzat S and Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 6:292–306. 2006. View Article : Google Scholar : PubMed/NCBI
5	Parameswaran R, Brooks S and Sadler GP: Molecular pathogenesis of follicular cell derived thyroid cancers. Int J Surg. 8:186–193. 2010. View Article : Google Scholar : PubMed/NCBI
6	Barakate DM: Thyroid cancer prognosis. Thyroid Clinic Sydney. http://www.thyroid.com.au/thyroid-cancer/thyroid-cancer-prognosis/2015. Accessed Sept 3. 2015.
7	Conzo G, Docimo G, Mauriello C, Gambardella C, Esposito D, Cavallo F, Tartaglia E, Napolitano S and Santini L: The current status of lymph node dissection in the treatment of papillary thyroid cancer. A literature review Clin Ter. 164:e343–e346. 2013.
8	Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, et al American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 19:1167–1214. 2009. View Article : Google Scholar : PubMed/NCBI
9	Hall TL, Layfield LJ, Philippe A and Rosenthal DL: Sources of diagnostic error in fine needle aspiration of the thyroid. Cancer. 63:718–725. 1989. View Article : Google Scholar : PubMed/NCBI
10	Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH and Kebebew E: Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg. 34:2589–2594. 2010. View Article : Google Scholar : PubMed/NCBI
11	Krause K, Jessnitzer B and Fuhrer D: Proteomics in thyroid tumor research. J Clin Endocrinol Metab. 94:2717–2724. 2009. View Article : Google Scholar : PubMed/NCBI
12	Fan Y, Shi L, Liu Q, Dong R, Zhang Q, Yang S, Fan Y, Yang H, Wu P, Yu J, et al: Discovery and identification of potential biomarkers of papillary thyroid carcinoma. Mol Cancer. 8:79–93. 2009. View Article : Google Scholar : PubMed/NCBI
13	Brown LM, Helmke SM, Hunsucker SW, Netea-Maier RT, Chiang SA, Heinz DE, Shroyer KR, Duncan MW and Haugen BR: Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol Carcinog. 45:613–626. 2006. View Article : Google Scholar : PubMed/NCBI
14	Giusti L, Iacconi P, Ciregia F, Giannaccini G, Donatini GL, Basolo F, Miccoli P, Pinchera A and Lucacchini A: Fine-needle aspiration of thyroid nodules: Proteomic analysis to identify cancer biomarkers. J Proteome Res. 7:4079–4088. 2008. View Article : Google Scholar : PubMed/NCBI
15	Subhasitanont P, Srisomsap C, Punyarit P and Svasti J: Proteomic studies of galectin-3 expression in human thyroid diseases by immunodetection. Cancer Genomics Proteomics. 3:389–394. 2006.
16	Srisomsap C, Subhasitanont P, Otto A, Mueller EC, Punyarit P, Wittmann-Liebold B and Svasti J: Detection of cathepsin B up-regulation in neoplastic thyroid tissues by proteomic analysis. Proteomics. 2:706–712. 2002. View Article : Google Scholar : PubMed/NCBI
17	Griffith OL, Chiu CG, Gown AM, Jones SJ and Wiseman SM: Biomarker panel diagnosis of thyroid cancer: A critical review. Expert Rev Anticancer Ther. 8:1399–1413. 2008. View Article : Google Scholar : PubMed/NCBI
18	Feilchenfeldt J, Tötsch M, Sheu S-Y, Robert J, Spiliopoulos A, Frilling A, Schmid KW and Meier CA: Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry. Mod Pathol. 16:1117–1123. 2003. View Article : Google Scholar : PubMed/NCBI
19	Volante M, Bozzalla-Cassione F, Orlandi F and Papotti M: Diagnostic role of galectin-3 in follicular thyroid tumors. Virchows Arch. 444:309–312. 2004. View Article : Google Scholar : PubMed/NCBI
20	Kebebew E, Peng M, Reiff E and McMillan A: Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 106:2592–2597. 2006. View Article : Google Scholar : PubMed/NCBI
21	Scognamiglio T, Hyjek E, Kao J and Chen Y-T: Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol. 126:700–708. 2006. View Article : Google Scholar : PubMed/NCBI
22	Viglietto G and De Marco C: Molecular biology of thyroid cancer. Contemporary Aspects of Endocrinology. Diamanti-Kandarakis E: InTech; c2011, pp. 189–234. 2011, http://www.intechopen.com/books/contemporary-aspects-of-endocrinology/molecular-biology-of-thyroid-cancer.
23	Schlumberger MJ: Papillary and follicular thyroid carcinoma. N Engl J Med. 338:297–306. 1998. View Article : Google Scholar : PubMed/NCBI
24	Zaydfudim V, Feurer ID, Griffin MR and Phay JE: The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery. 144:1070–1077; discussion 1077–1078. 2008. View Article : Google Scholar : PubMed/NCBI
25	Woyach JA and Shah MH: New therapeutic advances in the management of progressive thyroid cancer. Endocr Relat Cancer. 16:715–731. 2009. View Article : Google Scholar : PubMed/NCBI
26	Morita N, Ikeda Y and Takami H: Clinical significance of p53 protein expression in papillary thyroid carcinoma. World J Surg. 32:2617–2622. 2008. View Article : Google Scholar : PubMed/NCBI
27	Grogan RH, Mitmaker EJ and Clark OH: The evolution of biomarkers in thyroid cancer-from mass screening to a personalized biosignature. Cancers (Basel). 2:885–912. 2010. View Article : Google Scholar
28	Kim JW and Dang CV: Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 30:142–150. 2005. View Article : Google Scholar : PubMed/NCBI
29	Capello M, Ferri-Borgogno S, Cappello P and Novelli F: α-Enolase: A promising therapeutic and diagnostic tumor target. FEBS J. 278:1064–1074. 2011. View Article : Google Scholar : PubMed/NCBI
30	Mikuriya K, Kuramitsu Y, Ryozawa S, Fujimoto M, Mori S, Oka M, Hamano K, Okita K, Sakaida I and Nakamura K: Expression of glycolytic enzymes is increased in pancreatic cancerous tissues as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. Int J Oncol. 30:849–855. 2007.PubMed/NCBI
31	Zhang XZ, Xiao ZF, Li C, Xiao ZQ, Yang F, Li DJ, Li MY, Li F and Chen ZC: Triosephosphate isomerase and peroxiredoxin 6, two novel serum markers for human lung squamous cell carcinoma. Cancer Sci. 100:2396–2401. 2009. View Article : Google Scholar : PubMed/NCBI
32	Chang YS, Wu W, Walsh G, Hong WK and Mao L: Enolase-α is frequently down-regulated in non-small cell lung cancer and predicts aggressive biological behavior. Clin Cancer Res. 9:3641–3644. 2003.PubMed/NCBI
33	Liu K-J and Shih N-Y: The role of enolase in tissue invasion and metastasis of pathogens and tumor cells. J Cancer Mol. 3:pp. 45–48. 2007, http://www.mupnet.com/jocm%203%282%29%2045-48.pdf.
34	Liaudet-Coopman E, Beaujouin M, Derocq D, Garcia M, Glondu-Lassis M, Laurent-Matha V, Prébois C, Rochefort H and Vignon F: Cathepsin D: Newly discovered functions of a longstanding aspartic protease in cancer and apoptosis. Cancer Lett. 237:167–179. 2006. View Article : Google Scholar
35	Dunn AD, Crutchfield HE and Dunn JT: Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. Endocrinology. 128:3073–3080. 1991. View Article : Google Scholar : PubMed/NCBI
36	Kraimps J-L, Métayé T, Millet C, Margerit D, Ingrand P, Goujon JM, Levillain P, Babin P, Begon F and Barbier J: Cathepsin D in normal and neoplastic thyroid tissues. Surgery. 118:1036–1040. 1995. View Article : Google Scholar : PubMed/NCBI
37	Lokman NA, Ween MP, Oehler MK and Ricciardelli C: The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron. 4:199–208. 2011. View Article : Google Scholar : PubMed/NCBI
38	Mussunoor S and Murray GI: The role of annexins in tumour development and progression. J Pathol. 216:131–140. 2008. View Article : Google Scholar : PubMed/NCBI
39	Bao H, Jiang M, Zhu M, Sheng F, Ruan J and Ruan C: Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol. 90:177–185. 2009. View Article : Google Scholar : PubMed/NCBI
40	Sidani M, Wessels D, Mouneimne G, Ghosh M, Goswami S, Sarmiento C, Wang W, Kuhl S, El-Sibai M, Backer JM, et al: Cofilin determines the migration behavior and turning frequency of metastatic cancer cells. J Cell Biol. 179:777–791. 2007. View Article : Google Scholar : PubMed/NCBI
41	Wang W, Eddy R and Condeelis J: The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer. 7:429–440. 2007. View Article : Google Scholar : PubMed/NCBI
42	Zhu B, Fukada K, Zhu H and Kyprianou N: Prohibitin and cofilin are intracellular effectors of transforming growth factor β signaling in human prostate cancer cells. Cancer Res. 66:8640–8647. 2006. View Article : Google Scholar : PubMed/NCBI
43	Maiti AK, Ghosh K, Chatterjee U, Chakrobarti S, Chatterjee S and Basu S: Epidermal growth factor receptor and proliferating cell nuclear antigen in astrocytomas. Neurol India. 56:456–462. 2008. View Article : Google Scholar
44	Cvejic D, Selemetjev S, Savin S, Paunovic I and Tatic S: Changes in the balance between proliferation and apoptosis during the progression of malignancy in thyroid tumours. Eur J Histochem. 53:65–71. 2009. View Article : Google Scholar : PubMed/NCBI
45	Feng L, Li M, Zhang Q-P, Piao Z-A, Wang Z-H and Lv S: Utility of BRAF protein overexpression in predicting the metastasis potential of papillary thyroid carcinoma. Oncol Lett. 2:59–63. 2011.PubMed/NCBI
46	Tomsig JL, Sohma H and Creutz CE: Calcium-dependent regulation of tumour necrosis factor-alpha receptor signalling by copine. Biochem J. 378:1089–1094. 2004. View Article : Google Scholar
47	Tomsig JL, Snyder SL and Creutz CE: Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif. J Biol Chem. 278:10048–10054. 2003. View Article : Google Scholar : PubMed/NCBI
48	Ramsey CS, Yeung F, Stoddard PB, Li D, Creutz CE and Mayo MW: Copine-I represses NF-kappaB transcription by endoproteolysis of p65. Oncogene. 27:3516–3526. 2008. View Article : Google Scholar : PubMed/NCBI
49	Parcellier A, Gurbuxani S, Schmitt E, Solary E and Garrido C: Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun. 304:505–512. 2003. View Article : Google Scholar : PubMed/NCBI
50	Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E and Kroemer G: Heat shock proteins 27 and 70: Anti-apoptotic proteins with tumorigenic properties. Cell Cycle. 5:2592–2601. 2006. View Article : Google Scholar : PubMed/NCBI
51	Lebret T, Watson RWG, Molinié V, O'Neill A, Gabriel C, Fitzpatrick JM and Botto H: Heat shock proteins HSP27, HSP60, HSP70, and HSP90: Expression in bladder carcinoma. Cancer. 98:970–977. 2003. View Article : Google Scholar : PubMed/NCBI
52	Paoli P, Giannoni E and Chiarugi P: Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 1833:3481–3498. 2013. View Article : Google Scholar : PubMed/NCBI