Advertisement

Seven genes for the prognostic prediction in patients with glioma

  • G.-H. ZhangEmail author
  • Q.-Y. Zhong
  • X.-X. Gou
  • E.-X. Fan
  • Y. Shuai
  • M.-N. Wu
  • G.-J. YueEmail author
Research article

Abstract

Purpose

Glioma is a common malignant tumor of the central nervous system, which is characterized by a low cure rate, high morbidity, and high recurrence rate. Consequently, it is imperative to explore some indicators for prognostic prediction in glioma.

Methods

We obtained glioma data from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were obtained by R software from TCGA data sets. Through Cox regression analysis, risk scores were obtained to assess the weighted gene-expression levels, which could predict the prognosis of patients with glioma. The validity and the prognostic value of this model in glioma were confirmed by the manifestation of receiver-operating characteristic (ROC) curves, area under the curve (AUC), and 5-year overall survival (OS).

Results

In total, 920 DEGs of transcriptome genes in glioma were extracted from the TCGA database. We identified a novel seven-gene signature associated with glioma. Among them, AL118505.1 and SMOC1 were positively related to the 5-year OS of patients with glioma, showing a better prognosis for glioma; however, RAB42, SHOX2, IGFBP2, HIST1H3G, and IGF2BP3 were negatively related to 5-year OS, displaying a worse prognosis. In addition, according to risk scores, AL118505.1 was also a protective factor, while others were risk factors. Furthermore, the expression levels of SHOX2, IGFBP2, and IGF2BP3 were significantly positively correlated with glioma grades. Receiver-operating characteristic (ROC) curve assessed the accuracy and sensitivity of the gene signature. Each of the seven genes for patients with the distribution of the risk score was presented in the heat map.

Conclusion

We identified a novel seven-gene signature in patients with glioma, which could be used as a predictor for the prognosis of patients with glioma in the future.

Keywords

Glioma TCGA A seven-gene signature Prognosis Risk score 

Notes

Funding

This study was financially supported by the National Natural Science Foundation of China (No. 81260370).

Compliance with ethical standards

Conflict of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study was approved by the Affiliated Hospital of Zunyi Medical University institutional review board (IRB).

Informed consent

We obtained data from TCGA network in our study. Informed consent has been obtained from all individual participants included in the study.

References

  1. 1.
    Li B, et al. The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression. PLoS One. 2011;6:e25631.CrossRefGoogle Scholar
  2. 2.
    Brandes AA, et al. Temozolomide as a second line systemic regimen in recurrent high—grade glioma a phase II study. Ann Oncol. 2001;129:255.CrossRefGoogle Scholar
  3. 3.
    Khasraw M, et al. Antiangiogenic therapy for high-grade glioma. Cochrane Datab Syst Rev. 2014;9:CD008218.Google Scholar
  4. 4.
    Omar AI. Tumor treating field therapy in combination with bevacizumab for the treatment of recurrent glioblastoma. J Vis Exp. 2014;92:e51638.Google Scholar
  5. 5.
    Louis DN, et al. The WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.CrossRefPubMedGoogle Scholar
  6. 6.
    Louis DN, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131:803–20.CrossRefPubMedGoogle Scholar
  7. 7.
    Turkalp, et al. IDH mutation in glioma: new insights and promises for the future. JAMA Neurol. 2014;71:1319–25.CrossRefPubMedGoogle Scholar
  8. 8.
    Akagi Y, et al. Reclassification of 400 consecutive glioma cases based on the revised 2016 WHO classification. Brain Tumor Pathol. 2018;35:81–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Zacher A, et al. Molecular diagnostics of gliomas using next generation sequencing of a glioma-tailored gene. Panel Brain Pathol. 2017;27:146–59.CrossRefPubMedGoogle Scholar
  10. 10.
    Li B, et al. CD133 in brain tumor: the prognostic factor. Oncotarget. 2017;8:11144–59.PubMedGoogle Scholar
  11. 11.
    Lu G, et al. Phospholipase C Beta 1: a candidate signature gene for proneural subtype high-grade. Glioma Mol Neurobiol. 2016;53:6511–25.CrossRefPubMedGoogle Scholar
  12. 12.
    Song WS, et al. Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells. J Chin Med Assoc. 2016;79:538–45.CrossRefPubMedGoogle Scholar
  13. 13.
    Okada I, et al. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011;88:30–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Mancini C, et al. A fetal case of microphthalmia and limb anomalies with abnormal neuronal migration associated with SMOC1 biallelic variants. Eur J Med Genet. 2018;S1769–7212:30397–8.Google Scholar
  15. 15.
    Blaschke RJ, et al. SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development. Proc Natl Acad Sci USA. 1998;95:2406–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Clement-Jones M, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet. 2000;9:695–702.CrossRefPubMedGoogle Scholar
  17. 17.
    Schmidt B, et al. SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates. BMC Cancer. 2010;10:600.CrossRefPubMedGoogle Scholar
  18. 18.
    Dietrich D, et al. DNA methylation of the homeobox genes PITX2 and SHOX2 predicts outcome innon-small-cell lung cancer patients. Diagn Mol Pathol. 2012;21:93–104.CrossRefPubMedGoogle Scholar
  19. 19.
    Yang T, et al. Elevated SHOX2 expression is associated with tumor recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013;20:S644–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Hong S, et al. SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition inducer in breast cancer cells. Neoplasia. 2014;16:e1–5.CrossRefGoogle Scholar
  21. 21.
    Köhnke M, et al. Rab GTPase prenylation hierarchy and its potential role in choroideremia disease. PLoS One. 2013;8:e81758.CrossRefPubMedGoogle Scholar
  22. 22.
    Wang H, et al. Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types. Mod Pathol. 2006;19:1149–56.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang Y, et al. IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton’s jelly of the umbilical cord via JNK and Akt signaling pathways. PLoS One. 2017;12:e0184182.CrossRefPubMedGoogle Scholar
  24. 24.
    Shynlova O, et al. Insulin-like growth factors and their binding proteins define specific phases of myometrial differentiation during pregnancy in the rat. Biol Reprod. 2007;76:571–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Villani RM, et al. Patched1 inhibits epidermal progenitor cell expansion and basal cell carcinoma formation by limiting Igfbp2 activity. Cancer Prev Res (Phila). 2010;3:1222–34.CrossRefGoogle Scholar
  26. 26.
    Cen WN, et al. The expression and biological information analysis of miR-375-3p in head and neck squamous cell carcinoma based on 1825 samples from GEO, TCGA, and peer-reviewed publications. Pathol Res Pract. 2018;214:1835–47.CrossRefPubMedGoogle Scholar
  27. 27.
    Castel D, et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130:815–27.CrossRefPubMedGoogle Scholar
  28. 28.
    Kalinina J, et al. Proteomics of gliomas: initial biomarker discovery and evolution of technology. Neuro Oncol. 2011;13:926–42.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Head and Neck OncologyAffiliated Hospital of Zunyi Medical UniversityZunyiPeople’s Republic of China

Personalised recommendations