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Spectrin repeat containing nuclear envelope 1 and forkhead box protein E1 are promising markers for the detection of colorectal cancer in blood.

Identifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utili... Full description

Journal Title: Cancer prevention research (Philadelphia Pa.), February 2015, Vol.8(2), pp.157-164
Main Author: Melotte, Veerle
Other Authors: Yi, Joo Mi , Lentjes, Marjolein H F M , Smits, Kim M , Van Neste, Leander , Niessen, Hanneke E C , Wouters, Kim A D , Louwagie, Joost , Schuebel, Kornel E , Herman, James G , Baylin, Stephen B , van Criekinge, Wim , Meijer, Gerrit A , Ahuja, Nita , van Engeland, Manon
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1940-6215 ; DOI: 10.1158/1940-6207.CAPR-14-0198
Link: http://search.proquest.com/docview/1652455223/?pq-origsite=primo
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title: Spectrin repeat containing nuclear envelope 1 and forkhead box protein E1 are promising markers for the detection of colorectal cancer in blood.
format: Article
creator:
  • Melotte, Veerle
  • Yi, Joo Mi
  • Lentjes, Marjolein H F M
  • Smits, Kim M
  • Van Neste, Leander
  • Niessen, Hanneke E C
  • Wouters, Kim A D
  • Louwagie, Joost
  • Schuebel, Kornel E
  • Herman, James G
  • Baylin, Stephen B
  • van Criekinge, Wim
  • Meijer, Gerrit A
  • Ahuja, Nita
  • van Engeland, Manon
subjects:
  • Aged–Blood
  • Area Under Curve–Genetics
  • Biomarkers, Tumor–Blood
  • Cell Line, Tumor–Genetics
  • Colorectal Neoplasms–Genetics
  • DNA Methylation–Blood
  • Female–Genetics
  • Forkhead Transcription Factors–Blood
  • Humans–Genetics
  • Male–Blood
  • Middle Aged–Genetics
  • Nerve Tissue Proteins–Genetics
  • Nuclear Proteins–Genetics
  • Promoter Regions, Genetic–Genetics
  • ROC Curve–Genetics
  • Real-Time Polymerase Chain Reaction–Genetics
  • Sensitivity and Specificity–Genetics
  • Transfection–Genetics
  • Biomarkers, Tumor
  • Foxe1 Protein, Human
ispartof: Cancer prevention research (Philadelphia, Pa.), February 2015, Vol.8(2), pp.157-164
description: Identifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utility of NDRG4, GATA5, and two additional markers [Forkhead box protein E1 (FOXE1) and spectrin repeat containing nuclear envelope 1 (SYNE1)] promoter methylation as biomarkers in plasma DNA. Quantitative methylation-specific PCR was performed on plasma DNA from 220 patients with colorectal cancer and 684 noncancer controls, divided in a training set and a test set. Receiver operating characteristic analysis was performed to measure the area under the curve of GATA5, NDRG4, SYNE1, and FOXE1 methylation. Functional assays were performed in SYNE1 and FOXE1 stably transfected cell lines. The sensitivity of NDRG4, GATA5, FOXE1, and SYNE1 methylation in all stages of colorectal cancer (154 cases, 444 controls) was 27% [95% confidence interval (CI), 20%-34%), 18% (95% CI, 12%-24%), 46% (95% CI, 38%-54%), and 47% (95% CI, 39%-55%), with a specificity of 95% (95% CI, 93%-97%), 99% (95% CI, 98%-100%), 93% (95% CI, 91%-95%), and 96% (95% CI, 94%-98%), respectively. Combining SYNE1 and FOXE1, increased the sensitivity to 56% (95% CI, 48%-64%), while the specificity decreased to 90% (95% CI, 87%-93%) in the training set and to 58% sensitivity (95% CI, 46%-70%) and 91% specificity (95% CI, 80%-100%) in a test set (66 cases, 240 controls). SYNE1 overexpression showed no major differences in cell proliferation, migration, and invasion compared with controls. Overexpression of FOXE1 significantly decreased the number of colonies in SW480 and HCT116 cell lines. Overall, our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection.
language: eng
source:
identifier: E-ISSN: 1940-6215 ; DOI: 10.1158/1940-6207.CAPR-14-0198
fulltext: fulltext
issn:
  • 19406215
  • 1940-6215
url: Link


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titleSpectrin repeat containing nuclear envelope 1 and forkhead box protein E1 are promising markers for the detection of colorectal cancer in blood.
creatorMelotte, Veerle ; Yi, Joo Mi ; Lentjes, Marjolein H F M ; Smits, Kim M ; Van Neste, Leander ; Niessen, Hanneke E C ; Wouters, Kim A D ; Louwagie, Joost ; Schuebel, Kornel E ; Herman, James G ; Baylin, Stephen B ; van Criekinge, Wim ; Meijer, Gerrit A ; Ahuja, Nita ; van Engeland, Manon
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ispartofCancer prevention research (Philadelphia, Pa.), February 2015, Vol.8(2), pp.157-164
identifierE-ISSN: 1940-6215 ; DOI: 10.1158/1940-6207.CAPR-14-0198
subjectAged–Blood ; Area Under Curve–Genetics ; Biomarkers, Tumor–Blood ; Cell Line, Tumor–Genetics ; Colorectal Neoplasms–Genetics ; DNA Methylation–Blood ; Female–Genetics ; Forkhead Transcription Factors–Blood ; Humans–Genetics ; Male–Blood ; Middle Aged–Genetics ; Nerve Tissue Proteins–Genetics ; Nuclear Proteins–Genetics ; Promoter Regions, Genetic–Genetics ; ROC Curve–Genetics ; Real-Time Polymerase Chain Reaction–Genetics ; Sensitivity and Specificity–Genetics ; Transfection–Genetics ; Biomarkers, Tumor ; Foxe1 Protein, Human
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descriptionIdentifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utility of NDRG4, GATA5, and two additional markers [Forkhead box protein E1 (FOXE1) and spectrin repeat containing nuclear envelope 1 (SYNE1)] promoter methylation as biomarkers in plasma DNA. Quantitative methylation-specific PCR was performed on plasma DNA from 220 patients with colorectal cancer and 684 noncancer controls, divided in a training set and a test set. Receiver operating characteristic analysis was performed to measure the area under the curve of GATA5, NDRG4, SYNE1, and FOXE1 methylation. Functional assays were performed in SYNE1 and FOXE1 stably transfected cell lines. The sensitivity of NDRG4, GATA5, FOXE1, and SYNE1 methylation in all stages of colorectal cancer (154 cases, 444 controls) was 27% [95% confidence interval (CI), 20%-34%), 18% (95% CI, 12%-24%), 46% (95% CI, 38%-54%), and 47% (95% CI, 39%-55%), with a specificity of 95% (95% CI, 93%-97%), 99% (95% CI, 98%-100%), 93% (95% CI, 91%-95%), and 96% (95% CI, 94%-98%), respectively. Combining SYNE1 and FOXE1, increased the sensitivity to 56% (95% CI, 48%-64%), while the specificity decreased to 90% (95% CI, 87%-93%) in the training set and to 58% sensitivity (95% CI, 46%-70%) and 91% specificity (95% CI, 80%-100%) in a test set (66 cases, 240 controls). SYNE1 overexpression showed no major differences in cell proliferation, migration, and invasion compared with controls. Overexpression of FOXE1 significantly decreased the number of colonies in SW480 and HCT116 cell lines. Overall, our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection.
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titleSpectrin repeat containing nuclear envelope 1 and forkhead box protein E1 are promising markers for the detection of colorectal cancer in blood.
authorMelotte, Veerle ; Yi, Joo Mi ; Lentjes, Marjolein H F M ; Smits, Kim M ; Van Neste, Leander ; Niessen, Hanneke E C ; Wouters, Kim A D ; Louwagie, Joost ; Schuebel, Kornel E ; Herman, James G ; Baylin, Stephen B ; van Criekinge, Wim ; Meijer, Gerrit A...
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