nach oben

Endocrine

Erschienen in:

22.07.2023 | Original Article

The expression of two immunosuppressive SIGLEC family molecules in papillary thyroid cancer and their effect on prognosis

verfasst von: Tiefeng Jin, Wei Wang, Luqi Ge, Xiang Li, Minghua Ge

Erschienen in: Endocrine | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Background

The thyroid cancer (THCA) subtype that occurs more frequently is papillary thyroid cancer (PTC). Despite a favorable postoperative outcome, traditional antitumor therapy does not offer ideal results for patients with metastasis, relapse, and radioiodine resistance. Recent studies demonstrated the remarkable effects of immune checkpoint inhibitors on solid tumors, of which the immunoglobulin superfamily member SIGLEC10 and SIGLEC15 act as novel immunotherapy targets for tumors. Nevertheless, their role in PTC prognosis is still indefinite.

Methods

Immunohistochemistry was utilized to examine the expression of SIGLEC10 and SIGLEC15 in 244 PTC tissue specimens. Then the expression correlation between the two was analyzed in normal tissues (NT), tumor cells (TC), and tumor stroma (TS), respectively. Subsequently, the retrospective data on patients with PTC were collected to examine whether the two immunosuppressive SIGLEC family members could affect their prognosis.

Results

We confirmed that TC expressed higher levels of SIGLEC10 than NT. However, SIGLEC10 was down-regulated in TS and predicted poor outcomes. Meanwhile, down-regulation of SIGLEC15 expression was observed in both TC and TS, indicating a favorable prognosis. PTC patients with both SIGLEC10-SIGLEC15+ expression in TC and TS had a significantly higher recurrence risk. The expression of SIGLEC10 in TS and SIGLEC15 in TC or TS was an independent predictor of PFS, and a positive correlation was shown between SIGLEC10 and SIGLEC15 expression in TS.

Conclusions

Therefore, our results indicate that SIGLEC10 and SIGLEC15 may be applied as significant prognostic markers for PTC and attractive targets for THCA immunotherapy.

H. Sung, J. Ferlay, R.L. Siegel et al. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). https://doi.org/10.3322/caac.21660CrossRefPubMed

H. Lim, S.S. Devesa, J.A. Sosa, D. Check, C.M. Kitahara, Trends in thyroid cancer incidence and mortality in the united states, 1974–2013. JAMA 317, 1338–1348 (2017). https://doi.org/10.1001/jama.2017.2719CrossRefPubMedPubMedCentral

D. Laha, N. Nilubol, M. Boufraqech, New therapies for advanced thyroid cancer. Front Endocrinol (Lausanne) 11, 82 (2020). https://doi.org/10.3389/fendo.2020.00082CrossRefPubMed

W.H. Fridman, F. Pagès, C. Sautès-Fridman, J. Galon, The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer 12, 298–306 (2012). https://doi.org/10.1038/nrc3245CrossRefPubMed

N.A. Giraldo, R. Sanchez-Salas, J.D. Peske et al. The clinical role of the tme in solid cancer. Br J. Cancer 120, 45–53 (2019). https://doi.org/10.1038/s41416-018-0327-zCrossRefPubMed

S. Maman, I.P. Witz, A history of exploring cancer in context. Nat. Rev. Cancer 18, 359–376 (2018). https://doi.org/10.1038/s41568-018-0006-7CrossRefPubMed

F. Klemm, J.A. Joyce, Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25, 198–213 (2015). https://doi.org/10.1016/j.tcb.2014.11.006CrossRefPubMed

G.L. Beatty, W.L. Gladney, Immune escape mechanisms as a guide for cancer immunotherapy. Clin. Cancer Res. 21, 687–692 (2015). https://doi.org/10.1158/1078-0432.Ccr-14-1860CrossRefPubMed

S.L. Topalian, C.G. Drake, D.M. Pardoll, Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell 27, 450–461 (2015). https://doi.org/10.1016/j.ccell.2015.03.001CrossRefPubMedPubMedCentral

10.

X. Hou, C. Chen, X. Lan, X. He, Unveiling the molecular features, relevant immune and clinical characteristics of siglec15 in thyroid cancer. Front Immunol 13, 975787 (2022). https://doi.org/10.3389/fimmu.2022.975787CrossRefPubMedPubMedCentral

11.

J. Capdevila, L.J. Wirth, T. Ernst et al. Pd-1 blockade in anaplastic thyroid carcinoma. J. Clin. Oncol. 38, 2620–2627 (2020). https://doi.org/10.1200/jco.19.02727CrossRefPubMedPubMedCentral

12.

S. Ahn, T.H. Kim, S.W. Kim et al. Comprehensive screening for pd-l1 expression in thyroid cancer. Endocr. Relat. Cancer 24, 97–106 (2017). https://doi.org/10.1530/erc-16-0421CrossRefPubMed

13.

Y. Jiang, X. Zhao, J. Fu, H. Wang, Progress and challenges in precise treatment of tumors with pd-1/pd-l1 blockade. Front Immunol 11, 339 (2020). https://doi.org/10.3389/fimmu.2020.00339CrossRefPubMedPubMedCentral

14.

M.S. Macauley, P.R. Crocker, J.C. Paulson, Siglec-mediated regulation of immune cell function in disease. Nat. Rev. Immunol 14, 653–666 (2014). https://doi.org/10.1038/nri3737CrossRefPubMedPubMedCentral

15.

A.A. Barkal, R.E. Brewer, M. Markovic et al. Cd24 signalling through macrophage siglec-10 is a target for cancer immunotherapy. Nature 572, 392–396 (2019). https://doi.org/10.1038/s41586-019-1456-0CrossRefPubMedPubMedCentral

16.

M.A. Stanczak, S.S. Siddiqui, M.P. Trefny et al. Self-associated molecular patterns mediate cancer immune evasion by engaging siglecs on t cells. J. Clin. Invest. 128, 4912–4923 (2018). https://doi.org/10.1172/jci120612CrossRefPubMedPubMedCentral

17.

S. van de Wall, K.C.M. Santegoets, E.J.H. van Houtum, C. Büll, G.J. Adema, Sialoglycans and siglecs can shape the tumor immune microenvironment. Trends Immunol 41, 274–285 (2020). https://doi.org/10.1016/j.it.2020.02.001CrossRefPubMed

18.

N. Xiao, X. Zhu, K. Li et al. Blocking siglec-10(hi) tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma. Exp. Hematol Oncol. 10, 36 (2021). https://doi.org/10.1186/s40164-021-00230-5CrossRefPubMedPubMedCentral

19.

H. Wang, Y. Feng, Y. Zhang et al. Siglec10-an immunosuppressor and negative predictor of survival prognosis in gliomas. Front Genet 13, 873655 (2022). https://doi.org/10.3389/fgene.2022.873655CrossRefPubMedPubMedCentral

20.

C. Zhang, J. Zhang, F. Liang et al. Innate immune checkpoint siglec10 in cancers: Mining of comprehensive omics data and validation in patient samples. Front Med. 16, 596–609 (2022). https://doi.org/10.1007/s11684-021-0868-zCrossRefPubMed

21.

B. Li, B. Zhang, X. Wang et al. Expression signature, prognosis value, and immune characteristics of siglec-15 identified by pan-cancer analysis. Oncoimmunology 9, 1807291 (2020). https://doi.org/10.1080/2162402x.2020.1807291CrossRefPubMedPubMedCentral

22.

R. Takamiya, K. Ohtsubo, S. Takamatsu, N. Taniguchi, T. Angata, The interaction between siglec-15 and tumor-associated sialyl-tn antigen enhances tgf-β secretion from monocytes/macrophages through the dap12-syk pathway. Glycobiology 23, 178–187 (2013). https://doi.org/10.1093/glycob/cws139CrossRefPubMed

23.

X. Hou, C. Chen, X. He, X. Lan, Siglec-15 silencing inhibits cell proliferation and promotes cell apoptosis by inhibiting stat1/stat3 signaling in anaplastic thyroid carcinoma. Dis Markers 2022, 1606404 (2022). https://doi.org/10.1155/2022/1606404CrossRefPubMedPubMedCentral

24.

Z. Tang, C. Li, B. Kang, G. Gao, C. Li, Z. Zhang, Gepia: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45, W98–w102 (2017). https://doi.org/10.1093/nar/gkx247CrossRefPubMedPubMedCentral

25.

S. Wen, Y. Luo, W. Wu et al. Identification of lipid metabolism-related genes as prognostic indicators in papillary thyroid cancer. Acta Biochim. Biophys Sin (Shanghai) 53, 1579–1589 (2021). https://doi.org/10.1093/abbs/gmab145CrossRefPubMed

26.

R. Qin, C. Li, X. Wang, Z. Zhong, C. Sun, Identification and validation of an immune-related prognostic signature and key gene in papillary thyroid carcinoma. Cancer Cell Int. 21, 378 (2021). https://doi.org/10.1186/s12935-021-02066-9CrossRefPubMedPubMedCentral

27.

V.P. Balachandran, M. Gonen, J.J. Smith, R.P. DeMatteo, Nomograms in oncology: More than meets the eye. Lancet Oncol 16, e173–e180 (2015). https://doi.org/10.1016/s1470-2045(14)71116-7CrossRefPubMedPubMedCentral

28.

M.A. Zeiger, E.B. Schneider, Braf v600e mutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer. Ann. Surg. Oncol. 20, 3–4 (2013). https://doi.org/10.1245/s10434-012-2614-xCrossRefPubMed

29.

J. Munday, S. Kerr, J. Ni et al. Identification, characterization and leucocyte expression of siglec-10, a novel human sialic acid-binding receptor. Biochem. J. 355, 489–497 (2001). https://doi.org/10.1042/0264-6021:3550489CrossRefPubMedPubMedCentral

30.

G. Whitney, S. Wang, H. Chang et al. A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to cd33. Eur. J. Biochem. 268, 6083–6096 (2001). https://doi.org/10.1046/j.0014-2956.2001.02543.xCrossRefPubMed

31.

S. Gao, X.Z. Liu, L.Y. Wu et al. Long-term elevated siglec-10 in cerebral spinal fluid heralds better prognosis for patients with aneurysmal subarachnoid hemorrhage. Dis Markers 2022, 5382100 (2022). https://doi.org/10.1155/2022/5382100CrossRefPubMedPubMedCentral

32.

T. Angata, Y. Tabuchi, K. Nakamura, M. Nakamura, Siglec-15: An immune system siglec conserved throughout vertebrate evolution. Glycobiology 17, 838–846 (2007). https://doi.org/10.1093/glycob/cwm049CrossRefPubMed

33.

Q.T. Li, Z.Z. Huang, Y.B. Chen et al. Integrative analysis of siglec-15 mrna in human cancers based on data mining. J. Cancer 11, 2453–2464 (2020). https://doi.org/10.7150/jca.38747CrossRefPubMedPubMedCentral

34.

M.W.L. Quirino, M.C. Pereira, M.F. Deodato de Souza et al. Immunopositivity for siglec-15 in gastric cancer and its association with clinical and pathological parameters. Eur. J. Histochem. 2021; 65. https://doi.org/10.4081/ejh.2021.3174.

35.

H. Liang, Q. Chen, Z. Hu et al. Siglec15 facilitates the progression of non-small cell lung cancer and is correlated with spinal metastasis. Ann. Transl. Med. 10, 281 (2022). https://doi.org/10.21037/atm-22-764CrossRefPubMedPubMedCentral

36.

X. Chen, S. Mo, Y. Zhang et al. Analysis of a novel immune checkpoint, siglec-15, in pancreatic ductal adenocarcinoma. J. Pathol Clin. Res. 8, 268–278 (2022). https://doi.org/10.1002/cjp2.260CrossRefPubMedPubMedCentral

37.

J. Wang, J. Sun, L.N. Liu et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat. Med. 25, 656–666 (2019). https://doi.org/10.1038/s41591-019-0374-xCrossRefPubMedPubMedCentral

38.

J.A. Fagin, S.A. Wells Jr., Biologic and clinical perspectives on thyroid cancer. N. Engl. J. Med. 375, 1054–1067 (2016). https://doi.org/10.1056/NEJMra1501993CrossRefPubMedPubMedCentral

39.

Q.J. Sheng, W.Y. Tian, X.G. Dou et al. Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma. World J. Gastrointest Oncol. 12, 1255–1271 (2020). https://doi.org/10.4251/wjgo.v12.i11.1255CrossRefPubMedPubMedCentral

Titel: The expression of two immunosuppressive SIGLEC family molecules in papillary thyroid cancer and their effect on prognosis
verfasst von: Tiefeng Jin
Wei Wang
Luqi Ge
Xiang Li
Minghua Ge
Publikationsdatum: 22.07.2023
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 3/2023
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03452-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

The expression of two immunosuppressive SIGLEC family molecules in papillary thyroid cancer and their effect on prognosis

Abstract

Background

Methods

Results

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2023

Steroidogenic activity of liposomal methylated resveratrol analog 3,4,5,4′-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model

Understanding the characteristics of idiopathic osteoporosis by a systematic review and meta-analysis

Incoherent optical fluctuation flowmetry for detecting limbs with hemodynamically significant stenoses in patients with type 2 diabetes

Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome

The clinicopathological features and prognosis of silent corticotroph tumors: an updated systematic review and meta-analysis

Chronic hypoparathyroidism is associated with increased cortical bone density evaluated using high-resolution peripheral quantitative computed tomography

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin