Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms' tumor.
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.
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Dongjian
D
Song
Department of Ultrasonography, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China.
Lifang
L
Yue
Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China.
Gang
G
Wu
School of Life Science, Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China.
Shanshan
S
Ma
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Lihua
L
Guo
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Heying
H
Yang
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Qiuliang
Q
Liu
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Da
D
Zhang
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Ziqiang
Z
Xia
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Lei
L
Wang
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Junjie
J
Zhang
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Wei
W
Zhao
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
Fei
F
Guo
Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Construction East Road 1, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China. w_jiaxiang@yeah.net.
Jiaxiang
J
Wang
D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D009396:Wilms Tumor / Q000175:diagnosis / Q000235:genetics*
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C484762:SIX2 protein, human
Biomarker; SIX2 gene; Wilms’ tumor