Tumor Biology

, Volume 36, Issue 10, pp 7591–7598 | Cite as

Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms’ tumor

  • Dongjian Song
  • Lifang Yue
  • Gang Wu
  • Shanshan Ma
  • Lihua Guo
  • Heying Yang
  • Qiuliang Liu
  • Da Zhang
  • Ziqiang Xia
  • Lei Wang
  • Junjie Zhang
  • Wei Zhao
  • Fei Guo
  • Jiaxiang Wang
Research Article


This study was designed to evaluate the utility of expression and DNA methylation patterns of the sine oculis homeobox homolog 2 (SIX2) gene in early diagnosis and prognosis of Wilms’ tumor (WT). Methylation-specific polymerase chain reaction (MSP), real-time quantitative polymerase chain reaction (qRT-PCR), receiver operating characteristic (ROC), and survival curve analyses were utilized to measure the expression and DNA methylation patterns of SIX2 in a cohort of WT tissues, with a view to assessing their diagnostic and prognostic value. Relative expression of SIX2 mRNA was higher, while the promoter methylation level was lower in the WT than control group (P < 0.05) and closely associated with poor survival prognosis of WT children (P < 0.05). Increased expression and decreased methylation of SIX2 were correlated with increasing tumor size, clinical stage, vascular invasion, and unfavorable histological differentiation (P < 0.05). ROC curve analysis showed areas under the curve (AUCs) of 0.579 for methylation and 0.917 for expression in WT venous blood, indicating higher diagnostic yield of preoperative SIX2 expression. The preoperative venous blood SIX2 expression level serves as an underlying biomarker for early diagnosis of WT. SIX2 overexpression and concomitantly decreased promoter methylation are significantly associated with poor survival of WT children.


SIX2 gene Wilms’ tumor Biomarker 



The authors are grateful to Pro. Lijun Wang from School of Foreign Languages of Zhengzhou University and International Science Editing for the language editing and polishing of this paper. This work was supported by a grant (No. 81172085) from the National Natural Science Foundation of China.

Author contributions

DS, LY, GW, SM, LG, HY, QL, DZ, ZX, LW, JZ, WZ, and FG conducted experiments. JW planned and supervised experiments. DS wrote the paper. All authors approved the final version of the manuscript.

Conflicts of interest


Supplementary material

13277_2015_3456_MOESM1_ESM.doc (37 kb)
Supplementary File 1 (DOC 37 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dongjian Song
    • 1
  • Lifang Yue
    • 2
  • Gang Wu
    • 3
  • Shanshan Ma
    • 4
  • Lihua Guo
    • 1
  • Heying Yang
    • 1
  • Qiuliang Liu
    • 1
  • Da Zhang
    • 1
  • Ziqiang Xia
    • 1
  • Lei Wang
    • 1
  • Junjie Zhang
    • 1
  • Wei Zhao
    • 1
  • Fei Guo
    • 1
  • Jiaxiang Wang
    • 1
  1. 1.Department of Pediatric SurgeryFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Department of UltrasonographyThird Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  3. 3.Department of Interventional RadiologyFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.School of Life ScienceZhengzhou UniversityZhengzhouChina

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