Horm Metab Res
DOI: 10.1055/a-2255-5718
Original Article: Endocrine Care
Wang Chun
1
Pathology, Peking University Shenzhen Hospital, Shenzhen,
China
,
Meiyin Lu
2
Graduate School, Shantou University Medical College, Shantou,
China
3
Department of Biobank, Shenzhen Baoan Womenʼs and Children's
Hospital, Shenzhen, China
,
Jiakang Chen
1
Pathology, Peking University Shenzhen Hospital, Shenzhen,
China
,
Jian Li
1
Pathology, Peking University Shenzhen Hospital, Shenzhen,
China
4
State Key Laboratory of Chemical Oncogenomics, Peking University
Shenzhen Graduate School, Shenzhen, China
› Author Affiliations
Funding Information
Open Research Fund of State Key Laboratory of Chemical Oncogenomics —
2021
Shenzhen Science and Technology Program — JCYJ20220531094017039
The Key Program for Clinical Research at Peking University Shenzhen Hospital
— LCYJZD2021009
› Further Information
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Abstract
Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates
the Th1 immune response. IL-18 exhibits anticancer activity and has been
evaluated in clinical trials as a potential cancer treatment. However, evidence
suggests that it may also facilitate the development and progression of some
cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not
been investigated. In this study, we found that the expression of IL-18 was
significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18
expression was closely associated with lymphovascular invasion and lymph node
metastases. Furthermore, compared to PTC patients with no nodal metastasis,
serum IL-18 levels were slightly increased in patients with 1–4 nodal
metastases and significantly elevated in patients with 5 or more nodal
metastases. The pro-metastatic effect of IL-18 may be attributed to the
simultaneous increase in the expression of S100A10, a known factor that is
linked to nodal metastasis in PTC. In addition, the activation of several
pathways, such as the intestinal immune network for lgA production and
Staphylococcus aureus infection, may be involved in the metastasis process.
Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore,
suppressing the function of IL-18 rather than enhancing it appears to be a
reasonable strategy for treating aggressive PTC.
Keywords
IL-18 -
papillary thyroid carcinoma -
serum -
lymph node metastasis -
S100A10
Publication History
Received: 18 October 2023
Accepted after revision: 24 January 2024
Article published online:
14 February 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag
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Germany
References
1
Xu M,
Xi Z,
Zhao Q.
et al.
Causal inference between aggressive extrathyroidal extension and survival in
papillary thyroid cancer: a propensity score matching and weighting
analysis. Front Endocrinol (Lausanne) 2023; 14: 1149826
2
Tan LC,
Huang NS,
Yu PC.
et al.
Different clinicopathologic features predispose to different patterns of distant
metastasis with heterogeneous short-term prognosis in patients with
differentiated thyroid cancer. Clin Endocrinol (Oxf) 2022; 96: 402-412
3
Esmailbeig M,
Ghaderi A.
Interleukin-18: a regulator of cancer and autoimmune diseases. Eur Cytokine Netw 2017; 28: 127-140
4
Ihim SA,
Abubakar SD,
Zian Z.
et al.
Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: biological
role in induction, regulation, and treatment. Front Immunol 2022; 13: 919973
5
Shimizu M,
Takei S,
Mori M.
et al.
Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory
diseases. Front Immunol 2022; 13: 951535
6
Fang Y,
Tian S,
Pan Y.
et al.
Pyroptosis: a new frontier in cancer. Biomed Pharmacother 2020; 121: 109595
7
Fabbi M,
Carbotti G,
Ferrini S.
Context-dependent role of IL-18 in cancer biology and counter-regulation by
IL-18BP. J Leukoc Biol 2015; 97: 665-675
8
Iwasaki T,
Yamashita K,
Tsujimura T.
et al.
Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells
possibly through suppression of osteoclastic bone-resorption in nude mice. J Immunother 2002; 25: S52-S60
9
Nishio S,
Yamada N,
Ohyama H.
et al.
Enhanced suppression of pulmonary metastasis of malignant melanoma cells by
combined administration of alpha-galactosylceramide and interleukin-18. Cancer Sci 2008; 99: 113-120
10
Xu G,
Jiang XD,
Xu Y.
et al.
Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells
effectively suppresses the growth of glioma in rats. Cell Biol Int 2009; 33: 466-474
11
Srivastava S,
Pelloso D,
Feng H.
et al.
Effects of interleukin-18 on natural killer cells: costimulation of activation
through Fc receptors for immunoglobulin. Cancer Immunol Immunother 2013; 62: 1073-1082
12
Ye ZB,
Ma T,
Li H.
et al.
Expression and significance of intratumoral interleukin-12 and interleukin-18 in
human gastric carcinoma. World J Gastroenterol 2007; 13: 1747-1751
13
Ma T,
Kong M.
Interleukin-18 and -10 may be associated with lymph node metastasis in breast
cancer. Oncol Lett 2021; 21: 253
14
Xu L,
Zhu Y,
An H.
et al.
Clinical significance of tumor-derived IL-1beta and IL-18 in localized renal
cell carcinoma: associations with recurrence and survival. Urol Oncol 2015; 33: 68 e69-e16
15
Wang X,
Zhu YF,
Li DM.
et al.
Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune
thyroid diseases. Int J Immunogenet 2016; 43: 18-24
16
Jamshidi M,
Farnoosh G,
Mohammadi Pour S.
et al.
Genetic variants and risk of thyroid cancer among Iranian patients. Horm Mol Biol Clin Investig 2021; 42: 223-234
17
Lazow MA,
Fuller C,
Trout AT.
et al.
Immunohistochemical assessment and clinical, histopathologic, and molecular
correlates of membranous somatostatin type-2A receptor expression in high-risk
pediatric central nervous system tumors. Front Oncol 2022; 12: 996489
18
Masugi Y,
Yamazaki K,
Emoto K.
et al.
Upregulation of integrin beta4 promotes epithelial-mesenchymal transition and is
a novel prognostic marker in pancreatic ductal adenocarcinoma. Lab Invest 2015; 95: 308-319
19
Zhang Z,
Zhao S,
Wang K.
et al.
Identification of biomarkers associated with cervical lymph node metastasis in
papillary thyroid carcinoma: evidence from an integrated bioinformatic
analysis. Clin Hemorheol Microcirc 2021; 78: 117-126
20
Nipp M,
Elsner M,
Balluff B.
et al.
S100-A10, thioredoxin, and S100-A6 as biomarkers of papillary thyroid carcinoma
with lymph node metastasis identified by MALDI imaging. J Mol Med (Berl) 2012; 90: 163-174
21
Palma G,
Barbieri A,
Bimonte S.
et al.
Interleukin 18: friend or foe in cancer. Biochim Biophys Acta 2013; 1836: 296-303
22
Park H,
Byun D,
Kim TS.
et al.
Enhanced IL-18 expression in common skin tumors. Immunol Lett 2001; 79: 215-219
23
Terme M,
Ullrich E,
Aymeric L.
et al.
IL-18 induces PD-1-dependent immunosuppression in cancer. Cancer Res 2011; 71: 5393-5399
24
Kim J,
Kim C,
Kim TS.
et al.
IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK
pathway. Biochem Biophys Res Commun 2006; 344: 1284-1289
25
Kang JS,
Bae SY,
Kim HR.
et al.
Interleukin-18 increases metastasis and immune escape of stomach cancer via the
downregulation of CD70 and maintenance of CD44. Carcinogenesis 2009; 30: 1987-1996
26
Jiang DF,
Liu WL,
Lu YL.
et al.
Function of IL-18 in promoting metastasis of lung cancer. Zhonghua Zhong Liu Za Zhi 2003; 25: 348-352
27
Gunel N,
Coskun U,
Sancak B.
et al.
Prognostic value of serum IL-18 and nitric oxide activity in breast cancer
patients at operable stage. Am J Clin Oncol 2003; 26: 416-421
28
Li B,
Wang F,
Ma C.
et al.
Predictive value of IL-18 and IL-10 in the prognosis of patients with colorectal
cancer. Oncol Lett 2019; 18: 713-719
29
Diakowska D,
Markocka-Maczka K,
Grabowski K.
et al.
Serum interleukin-12 and interleukin-18 levels in patients with oesophageal
squamous cell carcinoma. Exp Oncol 2006; 28: 319-322
30
Okamoto M,
Azuma K,
Hoshino T.
et al.
Correlation of decreased survival and IL-18 in bone metastasis. Intern Med 2009; 48: 763-773
31
Ma R,
Yu Y,
Liu X.
et al.
Transcriptomic analysis of Nibea albiflora skin in response to infection by
cryptocaryon irritans. Fish Shellfish Immunol 2020; 98: 819-831
32
Wang S,
Li M,
Jiang Y.
et al.
Transcriptome analysis reveals immune regulation in the spleen of koi carp
(Cyprinus carpio Koi) during aeromonas hydrophila infection. Mol Immunol 2023; 162: 11-20
33
Zhan S,
Wang T,
Wang M.
et al.
In-depth proteomics analysis to identify biomarkers of papillary thyroid cancer
patients older than 45 years with different degrees of lymph node
metastases. Proteomics Clin Appl 2019; 13: e1900030
34
Bharadwaj A,
Kempster E,
Waisman DM.
The annexin A2/S100A10 complex: the mutualistic symbiosis of two
distinct proteins. Biomolecules 2021; 11: 1849
35
Kwon M,
MacLeod TJ,
Zhang Y.
et al.
S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen
receptors. Front Biosci 2005; 10: 300-325
36
Sowder AM,
Witt BL,
Hunt JP.
An update on the risk of lymph node metastasis for the follicular variant of
papillary thyroid carcinoma with the new diagnostic paradigm. Head Neck Pathol 2018; 12: 105-109
37
Raffaelli M,
De Crea C,
Sessa L.
et al.
Risk factors for central neck lymph node metastases in follicular variant vs.
classic papillary thyroid carcinoma. Endocrine 2018; 62: 64-70
38
Simpkins F,
Flores A,
Chu C.
et al.
Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in
recurrent ovarian cancer: a phase I dose-escalation study. . Cancer Immunol Res 2013; 1: 168-178
39
Robertson MJ,
Kline J,
Struemper H.
et al.
A dose-escalation study of recombinant human interleukin-18 in combination with
rituximab in patients with non-Hodgkin lymphoma. J Immunother 2013; 36: 331-341
40
Carbone A,
Vizio B,
Novarino A.
et al.
IL-18 paradox in pancreatic carcinoma: elevated serum levels of free IL-18 are
correlated with poor survival. J Immunother 2009; 32: 920-931
41
Lu G,
Chen L.
Cervical lymph node metastases in papillary thyroid cancer: Preoperative staging
with ultrasound and/or computed tomography. Medicine (Baltimore) 2022; 101: e28909
42
Wang R,
Tang Z,
Wu Z.
et al.
Construction and validation of nomograms to reduce completion thyroidectomy by
predicting lymph node metastasis in low-risk papillary thyroid carcinoma. Eur J Surg Oncol 2023; 49: 1395-1404
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