Annexin A10 is a novel prognostic biomarker of papillary thyroid cancer

Abstract

Background

The incidence of thyroid cancer (TC) is increasing rapidly worldwide. The target therapy for papillary TC (PTC) is limited, and the studies of PTC prognostic biomarkers are not common. As a new member of annexin A (ANXA) family, the function and clinical significance of ANXA10 in PTC have not been well investigated.

Methods

Expressions of all the 12 ANXA members were detected with qPCR in 12 PTC tissues, and the ANXA10 mRNAs in PTCs and their adjacent normal thyroid tissues were compared. The subcellular location and expression of ANXA10 in 121 PTC patients were investigated with immunohistochemistry, which further classified the patients into subgroups with low or high ANXA10. The clinical significance and prognostic value of ANXA10 were estimated by analyzing its correlation with clinical factors and overall survival rates by the chi-squared test, univariate analyses, and multivariate analyses.

Results

ANXA10 had the highest expression in PTCs among all the ANXA members. Moreover, ANXA10 was significantly upregulated in PTC compared with normal thyroid tissues. The PTC patients with low and high expression of ANXA10 took up 70.25% (85/121) and 29.75% (36/121), respectively. ANXA10 expression was associated with tumor size, differentiation, and overall survival rates of PTC. ANXA10 was an independent prognostic biomarker predicting the poor outcome of PTC.

Conclusions

ANXA10 expression was upregulated in PTC, and it was an independent prognostic biomarker of PTC, suggesting that ANXA10 may be a promising target for individual treatment of ANXA10.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Singh Ospina N, Iniguez-Ariza NM, Castro MR (2020) Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment. BMJ 368:l6670. https://doi.org/10.1136/bmj.l6670

    Article  PubMed  Google Scholar 

  2. 2.

    Kitahara CM, Sosa JA (2016) The changing incidence of thyroid cancer. Nat Rev Endocrinol 12:646–653. https://doi.org/10.1038/nrendo.2016.110

    Article  PubMed  Google Scholar 

  3. 3.

    Vuong HG, Odate T, Duong UNP, Mochizuki K, Nakazawa T, Katoh R, Kondo T (2018) Prognostic importance of solid variant papillary thyroid carcinoma: a systematic review and meta-analysis. Head Neck 40:1588–1597. https://doi.org/10.1002/hed.25123

    Article  PubMed  Google Scholar 

  4. 4.

    Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82:331–371. https://doi.org/10.1152/physrev.00030.2001

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Gerke V, Creutz CE, Moss SE (2005) Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 6:449–461. https://doi.org/10.1038/nrm1661

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Schloer S, Pajonczyk D, Rescher U (2018) Annexins in translational research: hidden treasures to be found. Int J Mol Sci 19. https://doi.org/10.3390/ijms19061781

  7. 7.

    Sharma M, Annexin C (2019) A2 (ANX A2): an emerging biomarker and potential therapeutic target for aggressive cancers. Int J Cancer 144:2074–2081. https://doi.org/10.1002/ijc.31817

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Foo SL, Yap G, Cui J, Lim LHK (2019) Annexin-A1—a blessing or a curse in cancer? Trends Mol Med 25:315–327. https://doi.org/10.1016/j.molmed.2019.02.004

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Liu XJ, Liu WL, Yang FM, Yang XQ, Lu XF (2015) Hepatoma-derived growth factor predicts unfavorable prognosis of epithelial ovarian cancer. Onco Targets Ther 8:2101–2109. https://doi.org/10.2147/OTT.S85660

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Liu Z, Sun R, Zhang X, Qiu B, Chen T, Li Z, Xu Y, Zhang Z (2019) Transcription factor 7 promotes the progression of perihilar cholangiocarcinoma by inducing the transcription of c-Myc and FOS-like antigen 1. EBioMedicine 45:181–191. https://doi.org/10.1016/j.ebiom.2019.06.023

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Azim HA Jr, Peccatori FA, Brohée S, Branstetter D, Loi S, Viale G, Piccart M, Dougall WC, Pruneri G, Sotiriou C (2015) RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy. Breast Cancer Res 17:24. https://doi.org/10.1186/s13058-015-0538-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Yeo W, Chan SL, Mo FKF, Chu CM, Hui JWY, Tong JHM, Chan AWH, Koh J, Hui EP, Loong H, Lee K, Li L, Ma B, To KF, Yu SCH (2015) Phase I/II study of temsirolimus for patients with unresectable hepatocellular carcinoma (HCC)—a correlative study to explore potential biomarkers for response. BMC Cancer 15:395. https://doi.org/10.1186/s12885-015-1334-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Xu YF, Liu ZL, Pan C, Yang XQ, Ning SL, Liu HD, Guo S, Yu JM, Zhang ZL (2019) HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium. Oncogene 38:868–880. https://doi.org/10.1038/s41388-018-0485-8

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Raulf N, Lucarelli P, Thavaraj S, Brown S, Vicencio JM, Sauter T, Tavassoli M (2018) Annexin A1 regulates EGFR activity and alters EGFR-containing tumour-derived exosomes in head and neck cancers. Eur J Cancer 102:52–68. https://doi.org/10.1016/j.ejca.2018.07.123

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    de Graauw M, van Miltenburg MH, Schmidt MK, Pont C, Lalai R, Kartopawiro J, Pardali E, le Devedec SE, Smit VT, van der Wal A, van't Veer LJ, Cleton-Jansen AM, ten Dijke P, van de Water B (2010) Annexin A1 regulates TGF-beta signaling and promotes metastasis formation of basal-like breast cancer cells. Proc Natl Acad Sci U S A 107:6340–6345. https://doi.org/10.1073/pnas.0913360107

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Cheng TY, Wu MS, Lin JT, Lin MT, Shun CT, Huang HY, Hua KT, Kuo ML (2012) Annexin A1 is associated with gastric cancer survival and promotes gastric cancer cell invasiveness through the formyl peptide receptor/extracellular signal-regulated kinase/integrin beta-1-binding protein 1 pathway. Cancer 118:5757–5767. https://doi.org/10.1002/cncr.27565

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    van der Heijden AG, Mengual L, Lozano JJ, Ingelmo-Torres M, Ribal MJ, Fernández PL, Oosterwijk E, Schalken JA, Alcaraz A, Witjes JA (2016) A five-gene expression signature to predict progression in T1G3 bladder cancer. Eur J Cancer 64:127–136. https://doi.org/10.1016/j.ejca.2016.06.003

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Zhu J, Wu J, Pei X, Tan Z, Shi J, Lubman DM (2017) Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma. PLoS One 12:e0175039. https://doi.org/10.1371/journal.pone.0175039

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Lu SH, Yuan RH, Chen YL, Hsu HC, Jeng YM (2013) Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system. Histopathology 63:640–648. https://doi.org/10.1111/his.12229

    Article  PubMed  Google Scholar 

  20. 20.

    Macaron C, Lopez R, Pai RK, Burke CA (2016) Expression of annexin A10 in serrated polyps predicts the development of metachronous serrated polyps. Clin Transl Gastroenterol 7:e205. https://doi.org/10.1038/ctg.2016.60

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Sun R, Liu Z, Qiu B, Chen T, Li Z, Zhang X, Xu Y, Zhang Z (2019) Annexin10 promotes extrahepatic cholangiocarcinoma metastasis by facilitating EMT via PLA2G4A/PGE2/STAT3 pathway. EBioMedicine 47:142–155. https://doi.org/10.1016/j.ebiom.2019.08.062

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Perrier ND, Brierley JD, Tuttle RM (2018) Differentiated and anaplastic thyroid carcinoma: major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 68:55–63. https://doi.org/10.3322/caac.21439

    Article  PubMed  Google Scholar 

  23. 23.

    Giordano T, Genomic J (2018) Hallmarks of thyroid neoplasia. Annu Rev Pathol 13:141–162. https://doi.org/10.1146/annurev-pathol-121808-102139

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Bible KC, Ryder M (2016) Evolving molecularly targeted therapies for advanced-stage thyroid cancers. Nat Rev Clin Oncol 13:403–416. https://doi.org/10.1038/nrclinonc.2016.19

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Xiaofei Lu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Yang, M., Guo, Y. et al. Annexin A10 is a novel prognostic biomarker of papillary thyroid cancer. Ir J Med Sci 190, 59–65 (2021). https://doi.org/10.1007/s11845-020-02263-x

Download citation

Keywords

  • Annexin
  • Annexin A10
  • Biomarker
  • Papillary thyroid cancer
  • Prognosis