Skip to main content

Advertisement

SpringerLink
Log in

The prognostic significance of annexin A family in glioblastoma

  • Original Article
  • Published:
Irish Journal of Medical Science (1971 -) Aims and scope Submit manuscript

Abstract

Background

Glioblastoma (GBM) is the most common histological type of glioma, which has the most aggressive biological characters and the worst outcome. The targeted therapy of GBM requires more progression, and new biomarkers should be identified.

Materials and methods

In our study, we firstly retrieved the data of TCGA and compared the TPMs of all ANXAs in TCGA database. By quantitative PCR (qPCR), we detected the mRNA levels of ANXAs in 8 pairs of GBM tissues and their corresponding normal brain tissues. Moreover, we detected the expression of ANXAs in 118 cases of GBMs, and further evaluated their clinical significance by analyzing the correlation with clinicopathological factors, and estimated their prognostic significance with univariate and multivariate analyses.

Results

In the TCGA database, ANXA1, ANXA2, ANXA4, and ANXA5 had higher transcripts per million (TPMs) in GBM tissues compared with the normal brain tissues, while ANXA3 expression was downregulated in GBM tissues. With qPCR, ANXA1, ANXA2, and ANXA10 were verified to be the upregulated genes in GBM, but other ANXAs had no significant differences. ANXA2 and ANXA10, but not ANXA1, were correlated with poor prognosis of GBM and identified as independent prognostic biomarkers for poor outcome.

Conclusions

ANXA1, ANXA2, and ANXA10 are the upregulated genes in GBM. ANXA2 and ANXA10, but not ANXA1, are independent prognostic biomarkers indicating unfavorable outcome. Our results suggest that expression profiles based on ANXA10 expression may be a new classification system to predict prognosis of GBM patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Alexander BM, Cloughesy TF (2017) Adult glioblastoma. J Clin Oncol 35(21):2402–2409. https://doi.org/10.1200/JCO.2017.73.0119

    Article  CAS  PubMed  Google Scholar 

  2. Campos B, Olsen LR, Urup T, Poulsen HS (2016) A comprehensive profile of recurrent glioblastoma. Oncogene 35(45):5819–5825. https://doi.org/10.1038/onc.2016.85

    Article  CAS  PubMed  Google Scholar 

  3. Van Meir EG, Hadjipanayis CG, Norden AD et al (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60(3):166–193. https://doi.org/10.3322/caac.20069

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zanders ED, Svensson F, Bailey DS (2019) Therapy for glioblastoma: is it working? Drug Discov Today 24(5):1193–1201. https://doi.org/10.1016/j.drudis.2019.03.008

    Article  PubMed  Google Scholar 

  5. Le Rhun E, Preusser M, Roth P et al (2019) Molecular targeted therapy of glioblastoma. Cancer Treat Rev 80

  6. Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82(2):331–371. https://doi.org/10.1152/physrev.00030.2001

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Donnelly SR, Moss SE (1997) Annexins in the secretory pathway. Cell Mol Life Sci 53(6):533–538. https://doi.org/10.1007/s000180050068

    Article  CAS  PubMed  Google Scholar 

  9. Moss SE, Morgan RO (2004) The annexins. Genome Biol 5(4):219. https://doi.org/10.1186/gb-2004-5-4-219

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wei B, Guo C, Liu S, Sun MZ (2015) Annexin A4 and cancer. Clin Chim Acta 447:72–78. https://doi.org/10.1016/j.cca.2015.05.016

    Article  CAS  PubMed  Google Scholar 

  11. Xi Y, Ju R, Wang Y (2020) Roles of Annexin A protein family in autophagy regulation and therapy. Biomed Pharmacother 130:110591. https://doi.org/10.1016/j.biopha.2020.110591

    Article  CAS  PubMed  Google Scholar 

  12. Lu ZJ, Liu SY, Yao YQ et al (2011) The effect of miR-7 on behavior and global protein expression in glioma cell lines. Electrophoresis 32(24):3612–3620. https://doi.org/10.1002/elps.201100230

    Article  CAS  PubMed  Google Scholar 

  13. Maule F, Bresolin S, Rampazzo E et al (2016) Annexin 2A sustains glioblastoma cell dissemination and proliferation. Oncotarget 7(34):54632–54649. https://doi.org/10.18632/oncotarget.10565

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wu L, Yang L, Xiong Y et al (2014) Annexin A5 promotes invasion and chemoresistance to temozolomide in glioblastoma multiforme cells. Tumour Biol 35(12):12327–12337. https://doi.org/10.1007/s13277-014-2545-1

    Article  CAS  PubMed  Google Scholar 

  15. Wu W, Yu T, Wu Y et al (2019) The miR155HG/miR-185/ANXA2 loop contributes to glioblastoma growth and progression. J Exp Clin Cancer Res 38(1):133. https://doi.org/10.1186/s13046-019-1132-0

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xu YF, Liu ZL, Pan C et al (2019) HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium. Oncogene 38(6):868–880. https://doi.org/10.1038/s41388-018-0485-8

    Article  CAS  PubMed  Google Scholar 

  17. Chen T, Li K, Liu Z et al (2021) WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1alpha accumulation in Myc-dependent and independent pathways. Mol Ther. https://doi.org/10.1016/j.ymthe.2021.02.017

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li Z, Liu J, Chen T et al (2021) HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-Myc. J Exp Clin Cancer Res 40(1):86. https://doi.org/10.1186/s13046-021-01890-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liu X, Yang M, Guo Y, Lu X (2021) Annexin A10 is a novel prognostic biomarker of papillary thyroid cancer. Ir J Med Sci 190(1):59–65. https://doi.org/10.1007/s11845-020-02263-x

    Article  CAS  PubMed  Google Scholar 

  20. Tang Z, Li C, Kang B et al (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45(W1):W98–W102. https://doi.org/10.1093/nar/gkx247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cheng SX, Tu Y, Zhang S (2013) FoxM1 promotes glioma cells progression by up-regulating Anxa1 expression. PLoS ONE 8(8):e72376. https://doi.org/10.1371/journal.pone.0072376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Christensen MV, Hogdall CK, Jochumsen KM, Hogdall EVS (2018) Annexin A2 and cancer: a systematic review. Int J Oncol 52(1):5–18. https://doi.org/10.3892/ijo.2017.4197

    Article  CAS  PubMed  Google Scholar 

  23. Foo SL, Yap G, Cui J, Lim LHK (2019) Annexin-A1 - a blessing or a curse in cancer? Trends Mol Med 25(4):315–327. https://doi.org/10.1016/j.molmed.2019.02.004

    Article  CAS  PubMed  Google Scholar 

  24. Huang KS, Wallner BP, Mattaliano RJ et al (1986) Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Cell 46(2):191–199. https://doi.org/10.1016/0092-8674(86)90736-1

    Article  CAS  PubMed  Google Scholar 

  25. Hung MS, Chen YC, Lin P et al (2019). Cul4A modulates invasion and metastasis of lung cancer through regulation of ANXA10. Cancers (Basel) 11(5). https://doi.org/10.3390/cancers11050618

  26. Sun R, Liu Z, Qiu B et al (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 

  27. Tsai JH, Lin YL, Cheng YC et al (2015) Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma. Mod Pathol 28(2):268–278. https://doi.org/10.1038/modpathol.2014.96

    Article  CAS  PubMed  Google Scholar 

  28. Wang J, Zhao S, Wang F, Zhang Y (2019) Prognostic significance of increased expression of annexin A10 (ANXA10) in serous epithelial ovarian cancer. Med Sci Monit 25:5666–5673. https://doi.org/10.12659/MSM.915911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim J, Kim MA, Jee CD et al (2009) Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma. Int J Cancer 125(8):1842–1850. https://doi.org/10.1002/ijc.24541

    Article  CAS  PubMed  Google Scholar 

  30. Liu SH, Lin CY, Peng SY et al (2002) Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation. Am J Pathol 160(5):1831–1837. https://doi.org/10.1016/S0002-9440(10)61129-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schloer S, Pajonczyk D, Rescher U (2018). Annexins in translational research: hidden treasures to be found. Int J Mol Sci 19(6).  https://doi.org/10.3390/ijms19061781

  32. Gao H, Yu B, Yan Y et al (2013) Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis. J Neurosurg 118(4):846–853. https://doi.org/10.3171/2012.9.JNS112134

    Article  CAS  PubMed  Google Scholar 

  33. Schittenhelm J, Trautmann K, Tabatabai G et al (2009) Comparative analysis of annexin-1 in neuroepithelial tumors shows altered expression with the grade of malignancy but is not associated with survival. Mod Pathol 22(12):1600–1611. https://doi.org/10.1038/modpathol.2009.132

    Article  CAS  PubMed  Google Scholar 

  34. Lu SH, Yuan RH, Chen YL et al (2013) Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system. Histopathology 63(5):640–648. https://doi.org/10.1111/his.12229

    Article  PubMed  Google Scholar 

  35. Kim JK, Kim PJ, Jung KH et al (2010) Decreased expression of annexin A10 in gastric cancer and its overexpression in tumor cell growth suppression. Oncol Rep 24(3):607–612

    Article  CAS  Google Scholar 

  36. 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(12):e205. https://doi.org/10.1038/ctg.2016.60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ishikawa A, Kuraoka K, Zaitsu J et al (2020) Loss of annexin A10 expression is associated with poor prognosis in early gastric cancer. Acta Histochem Cytochem 53(5):113–119. https://doi.org/10.1267/ahc.20-00014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Munksgaard PP, Mansilla F, Brems Eskildsen AS et al (2011) Low ANXA10 expression is associated with disease aggressiveness in bladder cancer. Br J Cancer 105(9):1379–1387. https://doi.org/10.1038/bjc.2011.404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Arcone R, Arpaia G, Ruoppolo M et al (1993) Structural characterization of a biologically active human lipocortin 1 expressed in Escherichia coli. Eur J Biochem 211(1–2):347–355. https://doi.org/10.1111/j.1432-1033.1993.tb19904.x

    Article  CAS  PubMed  Google Scholar 

  40. Ernst S, Lange C, Wilbers A et al (2004) An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. J Immunol 172(12):7669–7676. https://doi.org/10.4049/jimmunol.172.12.7669

    Article  CAS  PubMed  Google Scholar 

  41. Leoni G, Neumann PA, Kamaly N et al (2015) Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest 125(3):1215–1227. https://doi.org/10.1172/JCI76693

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Neurology, Qingzhou People’ s Hosptial, Shandong, Weifang, China

    Hankun Xu

  2. Departments of Cardiology, Yidu Central Hosptial, Weifang, Shandong, China

    Xiaoqian Wu & Yingfei Dou

  3. Departments of Neurosurgery, the Second Hospital of Shandong First Medical University, 706 Taishan Road, Taian, 271000, Shandong, China

    Wei Zheng

Authors
  1. Hankun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoqian Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yingfei Dou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zheng.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethics committee of YIDU Central Hospital and Shandong First Medical University, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Hankun Xu and Xiaoqian Wu contribute equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Wu, X., Dou, Y. et al. The prognostic significance of annexin A family in glioblastoma. Ir J Med Sci 191, 1539–1547 (2022). https://doi.org/10.1007/s11845-021-02737-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11845-021-02737-6

Keywords

Search

Navigation