Tiroid Kanserlerinde Metabolik ve Genetik Değişiklikler

Özet

Metabolik yeniden düzenlemenin tümör oluşumu ve ilerlemesinde önemli bir özellik olduğu bilinmektedir. Tiroid kanseri (TK), öncelikle mitogenle aktive olan protein kinaz (MAPK) yolu tarafından yönlendirilen bir kanserdir. MAPK sinyal yolu (RET-RAS-RAF-MEK-ERK), TK gelişimi sırasında, birden fazla substratın fosforilasyonunu düzenleyerek tümör büyümesi, invazyonu, metastazı ve farklılaşmayı sağlamaktadır. Kanser dokusunda, enerji metabolizması düzensizdir ve bu özellik, kanser hücrelerinin hızlı çoğalması ve gelişimi için daha yüksek bir enerjiye ihtiyaç duymaları ile ilişkilidir. TCA döngüsü, ATP üreten ve biyosentez için öncüller sağlayan merkezi bir metabolik yoldur. TK hücrelerinde, hızlı bir glikolitik akış seviyesine katkıda bulunan birçok glikolitik enzimin ekspresyonlarında artışlar görülür. TK hücrelerinde, ayrıca, artan bir yağ asidi alımı vardır ve bu durum, kanser hücrelerinin artan enerji ihtiyacına destek olmaktadır. Glutamin ise, kanser hücreleri için önemli bir enerji ve karbon kaynağıdır. Eser elementler, hem tiroid hormon metabolizmasında yer alırlar, hem de tiroid fonksiyonundaki bozukluklar eser elementlerin kan ve dokulardaki düzeylerini değiştirebilir. Onkogenler, tiroid kanserinin metabolik yeniden düzenlenmesinde kritik rol oynarlar. Tiroid patolojisinde birçok genetik mutasyon ve hücre yüzey belirteçleri ayırıcı tanı için hedeflenmiştir. TK’larda birçok farklı genetik değişiklik gösterilmiş olup bunlardan en sık olanı BRAF mutasyonlarıdır. Kitabın bu bölümünde, tiroid karsinomlarında görülen metabolik değişiklikler üzerinde durularak güncel bilgilerin paylaşılması hedeflenmiştir.

Referanslar

WHO Classification of Tumours Online. Available online: https://tumourclassification.iarc.who.int/welcome/ (accessed on 8 January 2025).

Verburg, FA. Differentiated Thyroid Cancer: Diagnosis, Therapy, and Follow-Up. In Atlas of Thyroid and Neuroendocrine Tumor Markers; Giovanella, L., Ed.; Springer International Publishing: Cham, Switzerland, 2018; pp. 51–64. ISBN 978-3-319-62506-5.

Conzo G, Avenia N, Bellastella G, Candela G, de Bellis A, Esposito K, Pasquali D, Polistena A, Santini L, Sinisi AA. The Role of Surgery in the Current Management of Differentiated Thyroid Cancer. Endocrine. 2014;47:380-388.

Kitahara CM, Sosa JA. Understanding the Ever-Changing Incidence of Thyroid Cancer. Nat. Rev. Endocrinol. 2020;16:617-618.

Hlozek J, Pekova B, Rotnagl J, Hol R, Astl J. Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention-A Review. Biomedicines. 2022;10:1515.

Prete A, Borges de Souza P, Censi S, Muzza M, Nucci N, Sponziello M. Update on Fundamental Mechanisms of Thyroid Cancer. Front Endocrinol. 2020;11:102.

Sanchez-Ares M, Cameselle-Garcia S, Abdulkader-Nallib I, Rodriguez-Carnero G, Beiras-Sarasquete C, Punal-Rodriguez JA, et al. Susceptibility genes and chromosomal regions associated with non-syndromic familial non-medullary thyroid carcinoma: some pathogenetic and diagnostic keys. Front Endocrinol (Lausanne). 2022;13:829103.

Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mechanisms. Archives of Physiology and Biochemistry. 2008;114(1):71-83.

Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13: 184-199.

Çelik Z. İnvaziv folliküler varyant papiller tiroid karsinomu (fvptk), invaziv enkapsüle folliküler varyant papiller tiroid karsinomu (iefvptk) ve yeni bir antite olan papiller nükleer özellikli noninvaziv tiroid neoplazmlarında (nıftp) morfolojik ve immunhistokimyasal analiz. Uzmanlık Tezi. T.C. Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Patoloji Anabilim Dalı, Konya, 2018.

Ciampi R, Nikiforov YE. Mini review: Ret/ptc rearrangements and braf mutations in thyroid tumorigenesis. Endocrinology. 2007;148:936.

Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28(7):742-62.

Ju SH, Song M, Lim JL, Kang YE, Yi HS, Shong M. Metabolic Reprogramming in Thyroid Cancer. Endocrinol Metab. 2024;39:425-444. https://doi.org/10.3803/EnM.2023.1802

Jozwiak P, Krzeslak A, Pomorski L, Lipinska A. Expression of hypoxia-related glucose transporters GLUT1 and GLUT3 in benign, malignant and non-neoplastic thyroid lesions. Mol Med Rep. 2012;6:601-606.

Nahm JH, Kim HM, Koo JS. Glycolysis-related protein expression in thyroid cancer. Tumour Biol. 2017;39:1010428317695922.

Bao L, Xu T, Lu X, Huang P, Pan Z, Ge M. Metabolic reprogramming of thyroid cancer cells and crosstalk in their microenvironment. Front Oncol. 2021;11:773028.

Burrows N, Babur M, Resch J, Williams KJ, Brabant G. Hypoxia-inducible factor in thyroid carcinoma. J Thyroid Res. 2011;2011:762905.

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1-133.

Heydarzadeh S, Moshtaghie AA, Daneshpoor M, Hedayati M. Regulators of glucose uptake in thyroid cancer cell lines. Cell Commun Signal. 2020;18:83.

Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res. 2009;69:4885-4893.

Anderson NM, Mucka P, Kern JG, Feng H. The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell. 2018;9:216-237.

Delgado-Goni T, Miniotis MF, Wantuch S, Parkes HG, Marais R, Workman P, et al. The BRAF inhibitor vemurafenib activates mitochondrial metabolism and inhibits hyperpolarized pyruvate-lactate exchange in BRAF-mutant human melanoma cells. Mol Cancer Ther. 2016;15:2987-2999.

Nagayama Y, Hamada K. Reprogramming of cellular metabolism and its therapeutic applications in thyroid cancer. Metabolites. 2022;12:1214.

Liu CL, Hsu YC, Lee JJ, Chen MJ, Lin CH, Huang SY, et al. Targeting the pentose phosphate pathway increases reactive oxygen species and induces apoptosis in thyroid cancer cells. Mol Cell Endocrinol. 2020;499:110595.

Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 2010;35:427-33.

Wei Z, Liu X, Cheng C, Yu W, Yi P. Metabolism of amino acids in cancer. Front Cell Dev Biol 2021;8:603837.

Hafliger P, Graff J, Rubin M, Stooss A, Dettmer MS, Altmann KH, et al. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent Mouse model. J Exp Clin Cancer Res. 2018;37:234.

Davidson CD, Carr FE. Review of pharmacological inhibition of thyroid cancer metabolism. J Cancer Metastasis Treat. 2021;7:45.

Coelho RG, Fortunato RS, Carvalho DP. Metabolic reprogramming in thyroid carcinoma. Front Oncol. 2018;8:82.

Yang L, Venneti S, Nagrath D. Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng. 2017;19:163-194.

Kim HM, Lee YK, Koo JS. Expression of glutamine metabolism-related proteins in thyroid cancer. Oncotarget. 2016;7:53628-53641.

Baenke F, Chaneton B, Smith M, Van Den Broek N, Hogan K, Tang H, et al. Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells. Mol Oncol. 2016;10:73-84.

Lukasiewicz M, Zwara A, Kowalski J, Mika A, Hellmann A. The role of lipid metabolism disorders in the development of thyroid cancer. Int. J. Mol. Sci. 2024;25:7129. https://doi.org / 10. 3390 / ijms 25137129.

Calder PC. Functional roles of fatty acids and their effects on human health. J Parenter Enter Nutr. 2015;39:18–32.

Farrokhi Yekta R, Rezaie Tavirani M, Arefi Oskouie A, Mohajeri-Tehrani MR, Soroush AR. The metabolomics and lipidomics window into thyroid cancer research. Biomarkers. 2016;22:595-603.

Biswas P, Datta C, Rathi P, Bhattacharjee A. Fatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells. Prostaglandins Other Lipid Mediat. 2022;160:106637.

Guo S, Wang Y, Zhou D, Li Z. Significantly increased monounsaturated lipids relative to polyunsaturated lipids in six types of cancer microenvironment are observed by mass spectrometry imaging. Sci Rep. 2014;4:5959.

Jajin MG, Abooshahab R, Hooshmand K, Moradi A, Siadat SD, Mirzazadeh R, Chegini KG, Hedayati M. Gas chromatography-mass spectrometry-based untargeted metabolomics reveals metabolic perturbations in medullary thyroid carcinoma. Sci Rep. 2022;12:8397.

Lu J, Zhang Y, Sun M, Ding C, Zhang L, Kong Y, Cai M, Miccoli P, Ma C, Yue X. Multi-omics analysis of fatty acid metabolism in thyroid carcinoma. Front Oncol. 2021;11:737127.

Tian Y, Nie X, Xu S, Li Y, Huang T, Tang H, Wang Y. Integrative metabonomics as potential method for diagnosis of thyroid malignancy. Sci Rep. 2015, 5, 14869.

Wojakowska A, Chekan M, Marczak Ł, Polanski K, Lange D, Pietrowska M, Widlak P. Detection of metabolites discriminating subtypes of thyroid cancer: molecular profiling of FFPE samples using the GC/MS approach. Mol Cell Endocrinol. 2015;417:149-157.

Abooshahab R, Hooshmand K, Razavi SA, Gholami M, Sanoie M, Hedayati M. Plasma metabolic profiling of human thyroid nodules by gas chromatography-mass spectrometry (GC-MS)-based untargeted metabolomics. Front Cell Dev Biol. 2020, 8, 385.

Shang X, Zhong X, Tian X. Metabolomics of papillary thyroid carcinoma tissues: potential biomarkers for diagnosis and promising targets for therapy. Tumor Biol. 2016;37:11163-11175.

Stanley J, Neelamohan R, Suthagar E, Vengatesh G, Jayakumar J, Chandrasekaran M, Banu S, Aruldhas M. Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours. Hum Exp Toxicol. 2016;35:585-597.

Hosseini-Zijoud SM, Ebadi SA, Goodarzi MT, Hedayati M, Abbasalipourkabir R, Mahjoob MP. Lipid peroxidation and antioxidant status in patients with medullary thyroid carcinoma: a case-control study. J Clin Diagn Res. 2016;10:BC04-BC07.

Lopes NMD, Lens HHM, da Silva Brito WA, Bianchi JK, Marinello PC, Cecchini R, Armani A, Cecchini AL. Role of papillary thyroid carcinoma patients with Hashimoto thyroiditis: evaluation of oxidative stress and inflammatory markers. Clin Transl Oncol. 2022;24:2366-2378.

Ji B, Liu Y, Zhang P, Wang Y, Wang G. COX-2 expression and tumor angiogenesis in thyroid carcinoma patients among northeast chinese population-result of a single-center study. Int J Med Sci. 2012;9:237-242.

Lee HM, Baek SK, Kwon SY, Jung KY, Chae SW, Hwang SJ, Woo JS, Lee JY. Cyclooxygenase 1 and 2 expressions in the human thyroid gland. Eur Arch Oto-Rhino-Laryngol. 2006;263:199-204.

Parvathareddy SK, Siraj AK, Annaiyappanaidu P, Al-Sobhi SS, Al-Dayel F, Al-Kuraya KS. Prognostic significance of COX-2 over-expression in BRAF-mutated middle eastern papillary thyroid carcinoma. Int J Mol Sci. 2020;21:9498.

Sun L, Wei X, Liu X, Zhou D, Hu F, Zeng Y, Sun Y, Luo S, Zhang Y, Yi XP. Expression of prostaglandin E2 and EP receptors in human papillary thyroid carcinoma. Tumor Biol. 2016;37:4689-4697.

Siironen P, Ristimaki A, Nordling S, Louhimo J, Haapiainen R, Haglund C. Expression of COX-2 is increased with age in papillary thyroid cancer. Histopathology. 2004;44:490-497.

Kajita S, Ruebel KH, Casey MB, Nakamura N, Lloyd RV. Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth. Mod Pathol. 2005;18:221-227.

Kummer NT, Nowicki TS, Azzi JP, Reyes I, Iacob C, Xie S, Swati I, Darzynkiewicz Z, Gotlinger KH, Suslina N, et al. Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction. J Cell Biochem. 2012;113:1998-2008.

Reyes I, Reyes N, Suriano R, Iacob C, Suslina N, Policastro A, Moscatello, A, Schantz S, Tiwari RK, Geliebter J. Gene expression profiling identifies potential molecular markers of papillary thyroid carcinoma. Cancer Biomark. 2019;24:71-83.

Nigam S, Zafiriou M, Deva R, Ciccoli R, Roux-Van der Merwe R. Structure, biochemistry and biology of hepoxilins. FEBS J. 2007;274:3503-3512.

Prasad VVTS, Padma K. Non-synonymous polymorphism (Gln261Arg) of 12-lipoxygenase in colorectal and thyroid cancers. Fam Cancer. 2012;11:615-621.

Gallegos Vargas J, Sanchez Roldan J, Ronquillo Sanchez M, Carmona Aparicio L, Floriano Sanchez E, Cardenas Rodriguez N. Gene expression of CYP1A1 and its possible clinical application in thyroid cancer cases. Asian Pac J Cancer Prev. 2016;17:3477-3482.

Revilla G, Pons MdP, Baila-Rueda L, García-León A, Santos D, Cenarro A, Magalhaes M, Blanco RM, Moral A, Ignacio Pérez J, et al. Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness. Sci Rep. 2019;9:10260.

Strickaert A, Corbet C, Spinette SA, Craciun L, Dom G, Andry G, Larsimont D, Wattiez R, Dumont JE, Feron O, et al. Reprogramming of energy metabolism: increased expression and roles of pyruvate carboxylase in papillary thyroid cancer. Thyroid. 2019;29:845-857.

Yao Z, Yin P, Su D, Peng Z, Zhou L, Ma L, Guo W, Ma L, Xu G, Shi J, et al. Serum metabolic profiling and features of papillary thyroid carcinoma and nodular goiter. Mol Biosyst. 2011;7:2608.

Wang R, Cheng Y, Su D, Gong B, He X, Zhou X, Pang Z, Cheng L, Chen Y, Yao Z. Cpt1c regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions. J Cancer. 2017;8:3675-3681.

Lohse I, Reilly P, Zaugg K. The CPT1C 5′UTR contains a repressing upstream open reading frame that is regulated by cellular energy availability and AMPK. PLoS ONE. 2011;6:21486.

Valvo V, Iesato A, Kavanagh TR, Priolo C, Zsengeller Z, Pontecorvi A, Stillman IE, Burke SD, Liu X, Nucera C. Fine-tuning lipid metabolism by targeting mitochondria-associated acetyl-Coa-carboxylase 2 in BRAFV600E papillary thyroid carcinoma. Thyroid. 2021;31:1335-1358.

Enns L, Ladiges W. Mitochondrial redox signaling and cancer invasiveness. J Bioenerg Biomembr. 2012;44:635-638.

Nagayama Y, Hamada K. Reprogramming of cellular metabolism and its therapeutic applications in thyroid cancer. Metabolites. 2022;12:1214.

Choi US, Arndt T. Endocrine and neuroendocrine systems. In canine and feline cytopathology; Elsevier: Amsterdam, The Netherlands, 2023; pp. 596–617. ISBN 9780323683685.

Graceffa G, Patrone R, Vieni S, Campanella S, Calamia S, Laise I, Conzo G, Latteri M, Cipolla C. Association between Hashimoto’s thyroiditis and papillary thyroid carcinoma: A retrospective analysis of 305 patients. BMC Endocr Disord. 2019;19:26.

Boi F, Pani F, Cal PG, Lai ML, Mariotti S. High prevalence of papillary thyroid carcinoma in nodular Hashimoto’s thyroiditis at the first diagnosis and during the follow-up. J Endocrinol Invest. 2018;41:395-402.

Zhang Y, Qiu L, He C, Wang Y, Liu Y, Zhang D, Li Z. Serum unsaturated free fatty acids: A potential biomarker panel for differentiating benign thyroid diseases from thyroid cancer. J Cancer. 2015;6: 1276-1281.

Liu Y, Liu C, Pan Y, Zhou1 J, Ju H, Zhang Y. Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake. Cell Death Discovery. 2022;8:423. https://doi.org/10.1038/s41420-022-01214-y

Bao L, Xu T, Lu X, Huang P, Pan Z, Ge M. Metabolic reprogramming of thyroid cancer cells and cross talk in their microenvironment. Front Oncol. 2021;11:773028.

Lu J, Zhang Y, Sun M, Ding C, Zhang L, Kong Y, Cai M, Miccoli P, Ma C, Yue X. Fatty acid metabolism as a potential therapeutic target in thyroid carcinoma. SSRN Electron J. 2021;1-28.

Lu J, Zhang Y, Sun M, Ding C, Zhang L, Kong Y, Cai M, Miccoli P, Ma C, Yue X. Multi-omics analysis of fatty acid metabolism in thyroid carcinoma. Front Oncol. 2021;11:737127.

Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta (BBA)-Mol Cell Res. 2016;1863:2422-2435.

Biswas P, Datta C, Rathi P, Bhattacharjee A. Fatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells. Prostaglandins Other Lipid Mediat. 2022;160:106637.

Revilla G, Corcoy R, Moral A, Escolà-Gil JC, Mato E. Cross-talk between inflammatory mediators and the epithelial mesenchymal transition process in the development of thyroid carcinoma. Int J Mol Sci. 2019;20:2466.

Jiang N, Zhang Z, Chen X, Zhang G, Wang Y, Pan L, Yan C, Yang G, Zhao L, Han J, et al. Plasma lipidomics profiling reveals biomarkers for papillary thyroid cancer diagnosis. Front Cell Dev Biol. 2021;9:682269.

Makide K, Kitamura H, Sato Y, Okutani M, Aoki J. Emerging lysophospholipid mediators, lysophosphatidylserine, lysophosphatidylthreonine, lysophosphatidylethanolamine and lysophosphatidylglycerol. Prostaglandins Other Lipid Mediat. 2009;89:135-139.

Guo S, Qiu L, Wang Y, Qin X, Liu H, He M, Zhang Y, Li Z, Chen X. Tissue imaging and serum lipidomic profiling for screening potential biomarkers of thyroid tumors by matrix-assisted laser desorption/ionization-fourier transform ion cyclotron resonance mass spectrometry. Anal Bioanal Chem. 2014;406:4357-4370.

Hunkeler M, Hagmann A, Stuttfeld E, Chami M, Guri Y, Stahlberg H, Maier T. Structural basis for regulation of human acetyl-CoA carboxylase. Nature. 2018;558:470-474.

Valvo V, Iesato A, Kavanagh TR, Priolo C, Zsengeller Z, Pontecorvi A, Stillman IE, Burke SD, Liu X, Nucera C. Fine-tuning lipid metabolism by targeting mitochondria-associated acetyl-Coa-carboxylase 2 in BRAFV600E papillary thyroid carcinoma. Thyroid. 2021;31:1335-1358.

Liu C, Zhou X, Pan Y, Liu Y, Zhang Y. Pyruvate carboxylase promotes thyroid cancer aggressiveness through fatty acid synthesis. BMC Cancer. 2021;21:722.

Ishikawa S, Tateya I, Hayasaka T, Masaki N, Takizawa Y, Ohno S, Kojima T, Kitani Y, Kitamura M, Hirano S, et al. Increased expression of phosphatidylcholine (16:0/18:1) and (16:0/18:2) in thyroid papillary cancer. PLoS ONE. 2012;7:e48873.

Feng K, Ma R, Li H, Yin K, Du G, Chen X, Liu Z, Yin D. Upregulated SLC27A2/FATP2 in differentiated thyroid carcinoma promotes tumor proliferation and migration. J Clin Lab Anal. 2022;36:e24148.

Park WJ, Kothapalli KSD, Lawrence P, Tyburczy C, Brenna JT. An alternate pathway to long-chain polyunsaturates: The FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3. J Lipid Res. 2009;50:1195-1202.

Wang Z, Wang F. Construction and evaluation of a prognosis prediction model for thyroid carcinoma based on lipid metabolism-related genes. Neuro Endocrinol Lett. 2022;43:323-332.

Tian Y, Nie X, Xu S, Li Y, Huang T, Tang H, Wang Y. Integrative metabolomics as potential method for diagnosis of thyroid malignancy. Sci Rep. 2015;5:14869.

Huang LT, Li TJ, Li ML, Luo HY, Wang YB, Wang JH. Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells. BMC Complement Med Ther. 2023;23:130.

Zeng F, Huang L, Cheng X, Yang X, Li T, Feng G, Tang Y, Yang Y. Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer. Cancer Cell Int. 2018;18:151.

Huang H, Rusiecki J, Zhao N, Chen Y, Ma S, Yu H, Ward MH, Udelsman R, Zhang Y. Thyroid-stimulating hormone, thyroid hormones, and risk of papillary thyroid cancer: a nested case-control study. Cancer Epidemiol Biomark Prev. 2017;26:1209-1218.

Halada S, Casado-Medrano V, Baran JA, Lee J, Chinmay P, Bauer AJ, Franco AT. Hormonal cross-talk between thyroid and breast cancer. Endocrinology. 2022;163:bqac075.

Diep Nguyen, T. Adiponectin: role in physiology and pathophysiology. Int J Prev Med. 2020;11:136.

Franchini F, Palatucci G, Colao A, Ungaro P, Macchia PE, Nettore IC. Obesity and thyroid cancer risk: an update. Int J Environ Res Public Health. 2022;19:1116.

Tirosh A, Shimon I. Complications of acromegaly: thyroid and colon. Pituitary. 2017;20(1):70-75. doi: 10.1007/s11102-016-0744-z.

Guo L, Wang C, Chi C,Wang X, Liu S, Zhao W, et al. Exhaled breath volatile biomarker analysis for thyroid cancer. Transl Res. 2015;166(2):188-95.

Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mechanisms. Archives of Physiology and Biochemistry. 2008;114(1):71-83.

Fan YL, Li XQ. Expression of leptin and its receptor in thyroid carcinoma: distinctive prognostic significance in different subtypes. Clinical Endocrinology. 2015;83(2):261-267.

Waser B, Beetschen K, Pellegata NS, Reubi JC. Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy. Neuroendocrinology. 2011;94(4):291-301.

Pappa T, Alevizaki M. Obesity and thyroid cancer: a clinical update. Thyroid. 2014;24(2):190-9. doi: 10.1089/thy.2013.0232.

Shin HY, Jee YH, Cho ER. Body mass index and incidence of thyroid cancer in Korea: the Korean Cancer Prevention Study-II. J Cancer Res Clin Oncol. 2017;143(1):143-149. doi: 10.1007/s00432-016-2261-x.

Kitahara CM, Platz EA, Freeman LE, Hsing AW, Linet MS, Park Y et al. Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev. 2011;20(3):464-72. doi: 10.1158/1055-9965.EPI-10-1220.

Arthur JR, Beckett GJ. Thyroid function. Br Med Bull. 1999;55:658-68.

Ravaglia G, Forti P, Maioli F, Nesi B, Pratelli L, Savarino L, Cucinotta D, Cavalli G. Blood micronutrient and thyroid hormone concentrations in the oldest-old. J Clin Endocrinol Metab. 2000;85:2260-5.

Danforth E, Jr Burger AG. The impact of nutrition on thyroid hormone physiology and action. Annu Rev Nutr 1989;9:201-227.

Brandao-Neto J, Saturnino ACRD, Leite LD, de Mederios-Rocha ED, Marcos CMP, da Silva CAB, Marchini JS, de Rezende AA, Almeide MDG, Mederios ADC. Lack of acute zinc effect on thyrotropin-releasing hormone–stimulated thyroid-stimulating hormone secretion during oral zinc tolerance test in healthy men. Nutr Res. 2006;26:493-496.

Pekary AE, Lukaski HC, Mena I, Hershman JM. Processing of TRH precursor peptides in rat brain and pituitary is zinc dependent. Peptides. 1991;12:1025-1032.

Kucharzewski M, Braziewicz J, Majewska U, Gozdz S. Copper, zinc, and selenium in whole blood and thyroid tissue of people with various thyroid diseases. Biol Trace Elem Res. 2003;93:9-18.

Al-Sayer H, Mathew TC, Asfar S, Khourshed M, Al-Bader A, Behbehani A, Dashti H. Serum changes in trace elements during thyroid cancers. Mol Cell Biochem. 2004;260:1-5.

Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, et al. De-regulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000;275:21797-800.

Tambay V, Raymond VA, Bilodeau M. MYC rules: leading glutamine metabolism toward a distinct cancer cell phenotype. Cancers (Basel). 2021;13:4484.

Landa I, Cabanillas ME. Genomic alterations in thyroid cancer: biological and clinical insights. Nat Rev Endocrinol. 2024;20:93-110.

Moura MM, Cavaco BM, Leite V. RAS proto-oncogene in medullary thyroid carcinoma. Endocr Relat Cancer. 2015;22:235-252.

Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021;221:107753.

Li Z, Sun C, Qin Z. Metabolic reprogramming of cancerassociated fibroblasts and its effect on cancer cell reprogramming. Theranostics. 2021;11:8322-8336.

Wilde L, Roche M, Domingo-Vidal M, Tanson K, Philp N, Curry J, et al. Metabolic coupling and the Reverse Warburg Effect in cancer: implications for novel biomarker and anticancer agent development. Semin Oncol. 2017;44:198-203.

Curry JM, Tassone P, Cotzia P, Sprandio J, Luginbuhl A, Cognetti DM, et al. Multicompartment metabolism in papillary thyroid cancer. Laryngoscope. 2016;126:2410-2418.

Claiborne MD, Leone R. Differential glutamine metabolism in the tumor microenvironment: studies in diversity and heterogeneity: a mini-review. Front Oncol. 2022;12:1011191.

Fozzatti L, Alamino VA, Park S, Giusiano L, Volpini X, Zhao L, et al. Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression. Sci Rep. 2019;9:8028.

Lidonnici J, Santoro MM, Oberkersch RE. Cancer-induced metabolic rewiring of tumor endothelial cells. Cancers (Basel) 2022;14:2735.

Cantelmo AR, Conradi LC, Brajic A, Goveia J, Kalucka J, Pircher A, et al. Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell. 2016;30:968-85.

Carmona-Fontaine C, Deforet M, Akkari L, Thompson CB, Joyce JA, Xavier JB. Metabolic origins of spatial organization in the tumor microenvironment. Proc Natl Acad Sci U S A. 2017;114:2934-2939.

Yoo HC, Yu YC, Sung Y, Han JM. Glutamine reliance in cell metabolism. Exp Mol Med. 2020;52:1496-1516.

Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I, et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature. 2015;520:192-7.

Agani F, Jiang BH. Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTOR pathway in cancer. Curr Cancer Drug Targets. 2013;13:245-51.

Salemme V, Centonze G, Cavallo F, Defilippi P, Conti L. The crosstalk between tumor cells and the immune microenvironment in breast cancer: implications for immunotherapy. Front Oncol. 2021;11:610303.

Xia L, Oyang L, Lin J, Tan S, Han Y, Wu N, et al. The cancer metabolic reprogramming and immune response. Mol Cancer. 2021;20:28.

Cuyas E, Verdura S, Martin-Castillo B, Alarcon T, Lupu R, Bosch-Barrera J, et al. Tumor cell-intrinsic immunometabolism and precision nutrition in cancer immunotherapy. Cancers (Basel). 2020;12:1757.

Elia I, Haigis MC. Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism. Nat Metab. 2021;3:21-32.

Tie Y, Tang F, Wei YQ, Wei XW. Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets. J Hematol Oncol. 2022;15:61.

Park A, Lee Y, Kim MS, Kang YJ, Park YJ, Jung H, et al. Prostaglandin E2 secreted by thyroid cancer cells contributes to immune escape through the suppression of natural killer (NK) cell cytotoxicity and NK cell differentiation. Front Immunol. 2018;9:1859.

Rice CM, Davies LC, Subleski JJ, Maio N, Gonzalez-Cotto M, Andrews C, et al. Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression. Nat Commun. 2018;9:5099.

Arts RJ, Plantinga TS, Tuit S, Ulas T, Heinhuis B, Tesselaar M, et al. Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages. Oncoimmunology. 2016;5:e1229725.

Weinberg RA. Oncogenes, antioncogenes and the molecular basis of multistep carcinogenesis. Cancer Res. 1985;49:3713.

Lloyd R V, Buehler D, Khanafshar E. Papillary Thyroid Carcinoma Variants. Head Neck Pathol. 2018;5:51-56.

Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993;91:179-184.

Eberhardt NL, Grebe SK, McIver B, Reddi HV. The role of the PAX8/PPARgamma fusion oncogene in the patho¬genesis of follicular thyroid cancer. Mol Cell Endocrinol. 2010;321:50-56.

Jo YS, Lee JC, Li S, et al. Significance of the expression of major histocompatibility complex class II antigen, HLA-DR and -DQ, with recurrence of papillary thyroid cancer. Int J Cancer. 2008;122:785-790.

Hwang JH, Hwang JH, Chung HK, et al. CXC chemokine receptor 4 expression and function in human anaplastic thy¬roid cancer cells. J Clin Endocrinol Metab. 2003;88:408-416.

Liu D, Liu Z, Condouris S, Xing M. BRAF V600E main¬tains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells. J Clin Endo¬crinol Metab. 2007;92:2264-2271.

Lee SJ, Lee MH, Kim DW, et al. Cross-regulation between oncogenic BRAF(V600E) kinase and the MST1 pathway in papillary thyroid carcinoma. PLoS One. 2011;6:e16180.

Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12:245-262.

Xing M, Alzahrani AS, Carson KA, et al. Association be¬tween BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309:1493-1501.

Liu Z, Hou P, Ji M, et al. Highly prevalent genetic alter¬ations in receptor tyrosine kinases and phosphatidyli¬nositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab. 2008;93:3106-3116.

Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab. 2003;88:2745-2752.

Kim DW, Hwang JH, Suh JM, et al. RET/PTC (rearranged in transformation/papillary thyroid carcinomas) tyrosine kinase phosphorylates and activates phosphoinositi¬de-dependent kinase 1 (PDK1): an alternative phospha¬tidylinositol 3-kinase-independent pathway to activate PDK1. Mol Endocrinol. 2003;17:1382-1394.

Jung HS, Kim DW, Jo YS, et al. Regulation of protein ki¬nase B tyrosine phosphorylation by thyroid-specific onco¬genic RET/PTC kinases. Mol Endocrinol 2005;19:2748-2759.

Hwang JH, Kim DW, Suh JM, et al. Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thy¬roid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation. Mol Endocrinol. 2003;17:1155-1166.

Kim DW, Chung HK, Park KC, et al. Tumor suppressor LKB1 inhibits activation of signal transducer and activator of transcription 3 (STAT3) by thyroid oncogenic tyrosine kinase rearranged in transformation (RET)/papillary thy¬roid carcinoma (PTC). Mol Endocrinol. 2007;21:3039-3049.

Kim YR, Byun HS, Won M, et al. Modulatory role of phos¬pholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC. BMC Cancer. 2008;8:144.

Kim H, Suh JM, Hwang ES, et al. Thyrotropin-mediated repression of class II trans-activator expression in thy¬roid cells: involvement of STAT3 and suppressor of cyto¬kine signaling. J Immunol. 2003;171:616-627.

Suh JM, Song JH, Kim DW, et al. Regulation of the phos¬phatidylinositol 3-kinase, Akt/protein kinase B, FRAP/ mammalian target of rapamycin, and ribosomal S6 kinase 1 signaling pathways by thyroid-stimulating hormone (TSH) and stimulating type TSH receptor antibodies in the thyroid gland. J Biol Chem. 2003;278:21960-21971.

Kim DW, Jo YS, Jung HS, et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/pap¬illary thyroid cancer kinases. J Clin Endocrinol Metab. 2006;91:4070-4076.

Hwang ES, Kim DW, Hwang JH, et al. Regulation of sig¬nal transducer and activator of transcription 1 (STAT1) and STAT1-dependent genes by RET/PTC (rearranged in transformation/papillary thyroid carcinoma) oncogenic tyrosine kinases. Mol Endocrinol. 2004;18:2672-2684.

Bartoletti-Stella A, Salfi NC, Ceccarelli C, Attimonelli M, Romeo G, Gasparre G. Mitochondrial DNA mutations in oncocytic adnexal lacrimal glands of the conjunctiva. Arch Ophthalmol. 2011;129:664-666.

Pereira L, Soares P, Maximo V, Samuels DC. Somatic mi¬tochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of report¬ed somatic mtDNA mutations in tumors. BMC Cancer. 2012;12:53.

Gasparre G, Porcelli AM, Bonora E, et al. Disruptive mi¬tochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A. 2007;104:9001-9006.

Bonora E, Porcelli AM, Gasparre G, et al. Defective ox¬idative phosphorylation in thyroid oncocytic carcino¬ma is associated with pathogenic mitochondrial DNA mutations affecting complexes I and III. Cancer Res. 2006;66:6087-6096.

Maximo V, Soares P, Lima J, Cameselle-Teijeiro J, Sobrin¬ho-Simoes M. Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondri¬al DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors. Am J Pathol. 2002;160:1857-1865.

Rogounovitch TI, Saenko VA, Shimizu-Yoshida Y, et al. Large deletions in mitochondrial DNA in radiation-associ¬ated human thyroid tumors. Cancer Res. 2002;62:7031-7041.

Berho M, Suster S. The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic study of 15 cases. Hum Pathol. 1997;28:47-53.

Hong JH, Yi HS, Yi S, Kim HW, Lee J, Kim KS. Implica¬tions of oncocytic change in papillary thyroid cancer. Clin Endocrinol (Oxf ). 2016;85:797-804.

Le Pennec S, Mirebeau-Prunier D, Boutet-Bouzamondo N, et al. Nitric oxide and calcium participate in the fine reg¬ulation of mitochondrial biogenesis in follicular thyroid carcinoma cells. J Biol Chem. 2011;286:18229-18239.

Raharijaona M, Le Pennec S, Poirier J, et al. PGC-1-related coactivator modulates mitochondrial-nuclear crosstalk through endogenous nitric oxide in a cellular model of oncocytic thyroid tumours. PLoS One. 2009;4:e7964.

Ferreira-da-Silva A, Valacca C, Rios E, et al. Mitochondri¬al dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration. PLoS One. 2015;10:e0122308.

Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008;21 Suppl 2:37-43.

Chiappetta G, Toti P, Cetta F, et al. The RET/PTC onco¬gene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J Clin Endocrinol Metab. 2002;87:364-369.

Hwang JH, Kim DW, Suh JM, et al. Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thy¬roid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation. Mol Endocrinol. 2003;17:1155-1166.

Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science. 2009;324:1713-1716.

Kim DW, Chung HK, Park KC, et al. Tumor suppressor LKB1 inhibits activation of signal transducer and activator of transcription 3 (STAT3) by thyroid oncogenic tyrosine kinase rearranged in transformation (RET)/papillary thy¬roid carcinoma (PTC). Mol Endocrinol. 2007;21:3039-3049.

Couto JP, Daly L, Almeida A, et al. STAT3 negatively reg¬ulates thyroid tumorigenesis. Proc Natl Acad Sci U S A. 2012;109:E2361-E2370.

Lee MH, Lee SE, Kim DW, et al. Mitochondrial localiza¬tion and regulation of BRAFV600E in thyroid cancer: a clinically used RAF inhibitor is unable to block the mi¬tochondrial activities of BRAFV600E. J Clin Endocrinol Metab. 2011;96:E19-E30.

Xing M. Genetic alterations in the phosphatidylinosi¬tol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010;20:697-706.

Liu Z, Hou P, Ji M, et al. Highly prevalent genetic alter¬ations in receptor tyrosine kinases and phosphatidyli¬nositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab. 2008;93:3106-3116.

Abubaker J, Jehan Z, Bavi P, et al. Clinicopathological analysis of papillary thyroid cancer with PIK3CA alter¬ations in a Middle Eastern population. J Clin Endocrinol Metab. 2008;93:611-618.

Hu Y, Lu W, Chen G, et al. K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Res. 2012;22:399-412.

Compton S, Kim C, Griner NB, et al. Mitochondrial dys¬function impairs tumor suppressor p53 expression/func¬tion. J Biol Chem. 2011;286:20297-20312.

Ni Y, He X, Chen J, et al. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. 2012;21:300-310.

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