Diagnostic and prognostic role of cell‐free DNA testing for colorectal cancer patients

Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and...

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Bibliographic Details
Published inInternational journal of cancer Vol. 140; no. 8; pp. 1888 - 1898
Main Authors Bedin, Chiara, Enzo, Maria Vittoria, Del Bianco, Paola, Pucciarelli, Salvatore, Nitti, Donato, Agostini, Marco
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 15.04.2017
Subjects
Adenoma
Aged
Alu Elements - genetics
ALU‐based
Biomarkers, Tumor - blood
Biopsy
Cancer
cell‐free DNA
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - blood
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
DNA, Neoplasm - blood
DNA, Neoplasm - genetics
Epigenesis, Genetic
Female
Frizzled-related protein 1
Humans
liquid biopsy
Male
Medical prognosis
Medical research
Medical screening
methylation
Middle Aged
Prognosis
Promoter Regions, Genetic
Tumors
ALU-based
cell-free DNA
colorectal cancer
methylation
liquid biopsy
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Abstract Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. What's new? Liquid biopsy of circulating cell‐free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor‐derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.
AbstractList Circulating cell-free DNA (cfDNA) was found in increased amounts in cancer patients and tumor-associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU-based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type-specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease.Circulating cell-free DNA (cfDNA) was found in increased amounts in cancer patients and tumor-associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU-based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type-specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease.
Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease.
Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. What's new? Liquid biopsy of circulating cell‐free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor‐derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.
Circulating cell-free DNA (cfDNA) was found in increased amounts in cancer patients and tumor-associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU-based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n=114) in comparison to healthy subjects (n=56) and patients with adenomatous lesions (n=22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type-specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. What's new? Liquid biopsy of circulating cell-free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor-derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.
Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients ( n  = 114) in comparison to healthy subjects ( n  = 56) and patients with adenomatous lesions ( n  = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. What's new? Liquid biopsy of circulating cell‐free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor‐derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.
Author Pucciarelli, Salvatore
Enzo, Maria Vittoria
Bedin, Chiara
Nitti, Donato
Del Bianco, Paola
Agostini, Marco
Author_xml – sequence: 1
  givenname: Chiara
  surname: Bedin
  fullname: Bedin, Chiara
  organization: Oncological and Gastroenterological Sciences, University of Padua
– sequence: 2
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  surname: Enzo
  fullname: Enzo, Maria Vittoria
  organization: Oncological and Gastroenterological Sciences, University of Padua
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  surname: Del Bianco
  fullname: Del Bianco, Paola
  organization: Veneto Oncological Institute – IRCSS
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  givenname: Salvatore
  surname: Pucciarelli
  fullname: Pucciarelli, Salvatore
  email: puc@unipd.it
  organization: Oncological and Gastroenterological Sciences, University of Padua
– sequence: 5
  givenname: Donato
  surname: Nitti
  fullname: Nitti, Donato
  organization: Oncological and Gastroenterological Sciences, University of Padua
– sequence: 6
  givenname: Marco
  surname: Agostini
  fullname: Agostini, Marco
  organization: The Methodist Hospital Research Institute
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27943272$$D View this record in MEDLINE/PubMed
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Fri Jul 25 09:29:03 EDT 2025
Sun Jul 13 05:11:19 EDT 2025
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Thu Apr 24 23:02:28 EDT 2025
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IsPeerReviewed true
IsScholarly true
Issue 8
Keywords ALU-based
cell-free DNA
colorectal cancer
methylation
liquid biopsy
Language English
License http://onlinelibrary.wiley.com/termsAndConditions#vor
2016 UICC.
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MergedId FETCHMERGED-LOGICAL-c4805-1594ee4e3ae3f0f58b7c0361379b0a32cff7cb74d481802ccf11d71e7a5858993
Notes Disclosures
The authors declare no conflict of interest.
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Snippet Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer...
Circulating cell-free DNA (cfDNA) was found in increased amounts in cancer patients and tumor-associated molecular alteration can be detected in cancer...
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pubmed
crossref
wiley
SourceType Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 1888
SubjectTerms Adenoma
Aged
Alu Elements - genetics
ALU‐based
Biomarkers, Tumor - blood
Biopsy
Cancer
cell‐free DNA
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - blood
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
DNA, Neoplasm - blood
DNA, Neoplasm - genetics
Epigenesis, Genetic
Female
Frizzled-related protein 1
Humans
liquid biopsy
Male
Medical prognosis
Medical research
Medical screening
methylation
Middle Aged
Prognosis
Promoter Regions, Genetic
Tumors
Title Diagnostic and prognostic role of cell‐free DNA testing for colorectal cancer patients
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fijc.30565
https://www.ncbi.nlm.nih.gov/pubmed/27943272
https://www.proquest.com/docview/1870817780
https://www.proquest.com/docview/2302292325
https://www.proquest.com/docview/1852662584
https://www.proquest.com/docview/1877838224
Volume 140
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