International Journal of Clinical Oncology

, Volume 22, Issue 4, pp 660–666 | Cite as

Tissue thioredoxin-interacting protein expression predicted recurrence in patients with meningiomas

Original Article



The redox regulatory protein, thioredoxin-interacting protein (TXNIP), has been confirmed as an important tumor suppressor gene in various types of human cancers. In previous studies, we found that overexpression of tumor suppressor gene RIZ1 in meningiomas can significantly improve the expression of TXNIP by microarray data analysis. Therefore, we hypothesized that TXNIP was associated with the initiation and progression of meningiomas.


First, we evaluated the expression of TXNIP and Ki-67 in meningioma tissues from 65 patients using immunohistochemistry. We also analyzed the correlation between TXNIP immunoreactivity and clinicopathological features, as well as patient prognostic factors.


According to immunohistochemistry results, high-grade meningioma tissues had significantly lower expression of TXNIP than benign meningioma tissues (29.31 ± 18.70 vs 74.61 ± 7.51, P < 0.0001). TXNIP and Ki67 were negatively correlated (P < 0.0001). Moreover, the expression of TXNIP was higher in nonrecurrent high-grade meningiomas (P < 0.05). In addition, Kaplan–Meier analysis indicated that expression of TXNIP and Ki-67 was related to recurrence-free time. Multivariate Cox analysis showed that TXNIP expression level was the only independent predictor for meningioma prognosis.


Our results demonstrated that high expression of TXNIP indicates a lower pathological grade of meningnioma, and is also associated with longer recurrence-free time. Therefore, TXNIP could be regarded as a potential molecular marker to predict recurrence in patients with meningiomas.


Meningioma TXNIP Recurrence 


  1. 1.
    Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820CrossRefPubMedGoogle Scholar
  2. 2.
    Soussain C, Ricard D, Fike JR et al (2009) CNS complications of radiotherapy and chemotherapy. Lancet 374:1639–1651CrossRefPubMedGoogle Scholar
  3. 3.
    Maier H, Ofner D, Hittmair A et al (1992) Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance. J Neurosurg 77:616–623CrossRefPubMedGoogle Scholar
  4. 4.
    Wen PY, Quant E, Drappatz J et al (2010) Medical therapies for meningiomas. J Neurooncol 99:365–378CrossRefPubMedGoogle Scholar
  5. 5.
    Zhou J, Yu Q, Chng WJ (2011) TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. Int J Biochem Cell Biol 43:1668–1673CrossRefPubMedGoogle Scholar
  6. 6.
    Lee JH, Jeong EG, Choi MC et al (2010) Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells. Mol Cells 30:107–112CrossRefPubMedGoogle Scholar
  7. 7.
    Ding MH, Wang Z, Jiang L et al (2015) The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas. Biomaterials 56:165–178CrossRefPubMedGoogle Scholar
  8. 8.
    Kwon HJ, Won YS, Suh HW et al (2010) Vitamin D3 upregulated protein 1 suppresses TNF-alpha-induced NF-kappaB activation in hepatocarcinogenesis. J Immunol 185:3980–3989CrossRefPubMedGoogle Scholar
  9. 9.
    Ikarashi M, Takahashi Y, Ishii Y et al (2002) Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease. Anticancer Res 22:4045–4048PubMedGoogle Scholar
  10. 10.
    Butler LM, Zhou X, Xu WS et al (2002) The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci USA 99:11700–11705CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhou J, Bi C, Cheong LL et al (2011) The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML. Blood 118:2830–2839CrossRefPubMedGoogle Scholar
  12. 12.
    Wang Q, Fan SY, Qian J et al (2014) AKT2 expression in histopathologic grading and recurrence of meningiomas. Eur J Surg Oncol 40:1056–1061CrossRefPubMedGoogle Scholar
  13. 13.
    Kim SY, Suh HW, Chung JW et al (2007) Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases. Cell Mol Immunol 4:345–351PubMedGoogle Scholar
  14. 14.
    Han SH, Jeon JH, Ju HR et al (2003) VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene 22:4035–4046CrossRefPubMedGoogle Scholar
  15. 15.
    Yam CH, Fung TK, Poon RY (2002) Cyclin A in cell cycle control and cancer. Cell Mol Life Sci 59:1317–1326CrossRefPubMedGoogle Scholar
  16. 16.
    Nishinaka Y, Nishiyama A, Masutani H et al (2004) Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemogenesis. Cancer Res 64:1287–1292CrossRefPubMedGoogle Scholar
  17. 17.
    Jeon JH, Lee KN, Hwang CY et al (2005) Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1. Cancer Res 65:4485–4489CrossRefPubMedGoogle Scholar
  18. 18.
    Lee KN, Kang HS, Jeon JH et al (2005) VDUP1 is required for the development of natural killer cells. Immunity 22:195–208CrossRefPubMedGoogle Scholar
  19. 19.
    Barber MA, Zhang T, Gagne BA et al (2007) NK cells negatively regulate antigen presentation and tumor-specific CTLs in a syngeneic lymphoma model. J Immunol 178:6140–6147CrossRefPubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Zheng Cai
    • 1
  • Chenran Zhang
    • 1
    • 2
  • Yongxiang Zou
    • 1
  • Chengyin Lu
    • 1
  • Hongkang Hu
    • 1
  • Jun Qian
    • 1
  • Lei Jiang
    • 1
  • Guohan Hu
    • 1
  1. 1.Department of Neurosurgery, Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Department of Pediatric Neurosurgery, School of Medicine, Xinhua HospitalShanghai Jiao Tong UniversityShanghaiChina

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