Abstract
Background
The incidence of thyroid cancer is fast increasing in both adults and children. The pediatric thyroid cancer had often already progressed to a more advanced stage of the disease at diagnosis. Early detection of pediatric thyroid cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to be over-expressed in cancers of diverse histological origin and it facilitates tumorigenesis by promoting survival, growth, and metastasis.
Methods
The plasma Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24 healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC children was performed. The expression levels of Lcn2 and NFκB in PTC tissue and peri-carcinoma tissue of PTC children were measured through Western blot.
Results
The plasma concentration of Lcn2 was significantly elevated in pediatric PTC patients compared with healthy controls. Besides, the plasma Lcn2 concentration significantly correlated with clinical characteristics, NFκB level, and Ki-67 positive rate of nucleus in tissue of PTC.
Conclusion
This is the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer. Further studies are needed to explore the definite role and mechanism of Lcn2 in thyroid cancer, which will help to explore novel diagnostic or therapeutic strategies.
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References
Siegel R, Ma J, Zou Z et al (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29
Vergamini LB, Frazier AL, Abrantes FL et al (2014) Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr 164:1481–1485
Machac J (2016) Thyroid cancer in pediatrics. Endocrinol Metab Clin North Am 45:359–404
Niedziela M (2006) Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 13:427–453
Gharib H, Papini E (2007) Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin North Am 36:707–735
Romei C, Elisei R (2012) RET/PTC translocations and clinico-pathological features in human papillary thyroid carcinoma. Front Endocrinol (Lausanne) 3:54
Zimmerman D, Hay ID, Gough IR et al (1988) Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery 104:1157–1166
Alzahrani AS, Alkhafaji D, Tuli M et al (2016) Comparison of differentiated thyroid cancer in children and adolescents (≤ 20 years) with young adults. Clin Endocrinol (Oxf) 84:571–577
Rodvold JJ, Mahadevan NR, Zanetti M (2012) Lipocalin 2 in cancer: when good immunity goes bad. Cancer Lett 316:132–138
Roudkenar MH, Halabian R, Ghasemipour Z et al (2008) Neutrophil gelatinase-associated lipocalin acts as a protective factor against H2O2 toxicity. Arch Med Res 39:560–566
Lin HH, Liao CJ, Lee YC et al (2011) Lipocalin-2-induced cytokine production enhances endometrial carcinoma cell survival and migration. Int J Biol Sci 7:74–86
Lannetti A, Pacifico F, Acquaviva R et al (2008) The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. Proc Natl Acad Sci USA 105:14058–14063
Rosignolo F, Sponziello M, Durante C et al (2016) Expression of pax8 target genes in papillary thyroid carcinoma. Plos One 11:e0156658
Barresi V, Leni A, Tuccari G et al (2012) Neutrophil gelatinase-associated lipocalin (NGAL) immunohistochemical expression in follicular cell-derived thyroid tumors: a novel diagnostic tool? Histol Histopathol 27:329–336
Wang G, Ma N, Meng L et al (2015) Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation. Mol Cell Biochem 410:207–213
Lydiatt WM, Patel SG, O’Sullivan B et al (2017) Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67:122–137
Ahmed MW, Kayani MA, Shabbir G et al (2016) Expression of PTEN and its correlation with proliferation marker Ki-67 in head and neck cancer. Int J Biol Markers 31:e193–e203
Wang Y, Lam KS, Kraegen EW et al (2007) Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53:34–41
Goetz DH, Holmes MA, Borregaard N et al (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10:1033–1043
Nakamura I, Hama S, Itakura S et al (2014) Lipocalin2 as a plasma marker for tumors with hypoxic regions. Sci Rep 4:7235
Wang G, Liu X, Meng L et al (2014) Up-regulated lipocalin-2 in pulmonary hypertension involving in pulmonary artery SMC resistance to apoptosis. Int J Biol Sci 10:798–806
Wang G, Liu S, Wang L et al (2017) Lipocalin-2 promotes endoplasmic reticulum stress and proliferation by augmenting intracellular iron in human pulmonary artery smooth muscle cells. Int J Biol Sci 13:135–144
Chung TW, Choi HJ, Kim CH et al (2013) Lipocalin-2 elicited by advanced glycation end-products promotes the migration of vascular smooth muscle cells. Biochim Biophys Acta 1833:3386–3395
Lee EK, Kim HJ, Lee KJ et al (2011) Inhibition of the proliferation and invasion of hepatocellular carcinoma cells by lipocalin 2 through blockade of JNK and PI3K/Akt signaling. Int J Oncol 38:325–333
Volpe V, Raia Z, Sanguigno L (2013) NGAL controls the metastatic potential of anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab 98:228–235
Barresi V, Vitarelli E, Reggiani Bonetti L (2012) Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) immunoexpression in follicular-patterned lesions of the thyroid gland. Virchows Arch 460:319–325
Ma H, Xu S, Yan J et al (2014) The value of tumor markers in the diagnosis of papillary thyroid carcinoma alone and in combination. Pol J Pathol 65:202–209
Roli L, Pecoraro V, Trenti T (2017) Can NGAL be employed as prognostic and diagnostic biomarker in human cancers? A systematic review of current evidence. Int J Biol Markers 32:e53–e61
Gorman MF, Ji L, Ko RH et al (2010) Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): a Therapeutic Advances in Childhood Leukemia (TACL) Consortium study. Pediatr Blood Cancer 55:421–429
Cordioli MI, Moraes L, Cury AN et al (2015) Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma? Endocr Relat Cancer 22:R311–R324
Acknowledgements
We thank the otorhinolaryngology—head and neck surgery department of Beijing Children’s Hospital for providing human laryngeal tissue samples.
Funding
This work was supported by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (ZYLX201508) and Beijing Municipal Science and Technology Project (Z151100003715006).
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The authors declare that there are no conflicts of interest.
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The ethnics were approved by Beijing Children’s Hospital Ethics Committee. All human subjects or their parents (or legal guardians) had provided written informed consent.
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Tai, J., Wang, S., Zhang, J. et al. Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor clinical characteristics. Eur Arch Otorhinolaryngol 275, 2823–2828 (2018). https://doi.org/10.1007/s00405-018-5118-x
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DOI: https://doi.org/10.1007/s00405-018-5118-x