title: Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas.
abstract: OBJECTIVE
  To investigate GATA5, SFRP2, and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer (CRC) or adenomas.
  
  
  METHODS
  There were 57 CRC patients, 30 adenomas patients, and 47 control patients enrolled in this study. Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5, SFRP2, and ITGA4 genes in plasma DNA, and their association with clinical outcome in CRC. The predictive ability of GATA5, SFRP2, and ITGA4 methylation, individually or in combination, to detect CRC or adenomas was further analyzed.
  
  
  RESULTS
  Hypermethylated GATA5 was detected in plasma in 61.4% (35/57) of CRC cases, 43.33% (13/30) of adenoma cases, and 21.28% (10/47) of control cases. The hypermethylation of SFRP2 was detected in 54.39% (31/57), 40.00% (12/30), and 27.66% (13/47) in plasma samples from CRC, adenomas, and controls, respectively. ITGA4 methylation was detected in 36.84% (21/57) of plasma samples of CRC patients and in 30.00% (9/30) of plasma samples from patients with colorectal adenomas, and the specificity of this individual biomarker was 80.85% (9/47). Moreover, GATA5 methylation in the plasma was significantly correlated with larger tumor size (P = 0.019), differentiation status (P = 0.038), TNM stage (P = 0.008), and lymph node metastasis (P = 0.008). SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status (SFRP2, P = 0.012; ITGA4, P = 0.007), TNM stage (SFRP2, P = 0.034; ITGA4, P = 0.021), and lymph node metastasis (SFRP2, P = 0.034; ITGA4, P = 0.021). From the perspective of predictive power and cost-performance, using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC (OR = 8.06; 95%CI: 2.54-25.5; P < 0.01) and adenomas (OR = 3.35; 95%CI: 1.29-8.71; P = 0.012).
  
  
  CONCLUSIONS
  A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Song
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Hong-Na
authors.initials: HN
authors.lastname: Lu
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Dan-Ping
authors.initials: DP
authors.lastname: Wang
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Bei-Lei
authors.initials: BL
authors.lastname: Sun
authors.affiliation: Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Huang
mesh_terms: D000236:Adenoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D050992:GATA5 Transcription Factor / Q000097:blood / Q000235:genetics*; D006801:Humans; D039441:Integrin alpha4 / Q000097:blood / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D047368:Tumor Burden; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D014408:Biomarkers, Tumor; D050992:GATA5 Transcription Factor; D039441:Integrin alpha4; D008565:Membrane Proteins; C494755:GATA5 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins
keywords: Colorectal cancer; GATA binding protein 5; Hypermethylation; Integrin, alpha 4; Methylation-specific PCR; Secreted frizzled-related protein 2