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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Online
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1437-4331
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Volume 57, Issue 2

Issues

Urinary measurement of circulating tumor DNA for treatment monitoring and prognosis of metastatic colorectal cancer patients

Tao Song
  • Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Fei Mao
  • Department of Urology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Li Shi
  • Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Xuemei Xu
  • Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Zirong Wu
  • Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Juan Zhou
  • Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, P.R. China
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/ Meifang Xiao
  • Corresponding author
  • Center for Laboratory Medicine, Maternal and Child Health Hospital of Hainan Province, Longkun Road 75, 570206 Haikou, P.R. China
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Published Online: 2018-07-17 | DOI: https://doi.org/10.1515/cclm-2017-0675

Abstract

Background

Solid tumor tissue testing is the gold standard for molecular-based assays for metastatic colorectal cancer (mCRC). This poses challenges during treatment monitoring. Total DNA derived from urine specimens offers clear advantages to track the disease dynamics. Our study aims to evaluate the sensitivity for total DNA recovered from urine and its clinical relevance to mCRC.

Methods

KRAS mutations in urine specimens were examined in 150 mCRC patients. Baseline concordance was established to determined clinical relevance. The total DNA quantities were also prospectively examined in serial samplings during treatment.

Results

Analysis of the genetic mutations showed good agreement for baseline samples. Matched tumor and urine specimens’ molecular profiles were observed to have 90% concordance. Comparing with healthy volunteers, we established a cutoff of 8.15 ng that demonstrated elevated total DNA levels was associated with mCRC patients (sensitivity: 90.7%; specificity: 82.0%). For patients treated with chemotherapy or anti-epidermal growth factor receptor inhibitors, DNA quantity mirrored early treatment response. Survival analysis showed that patients with sustained elevated quantities of KRAS mutations had poorer outcome.

Conclusions

Total urine DNA offers a viable complement for mutation profiling in mCRC patients, given the good agreement with matched tumor samples. Our study also established that this is specific based on the results from healthy individuals. Serial monitoring of total DNA levels allowed early prediction to treatment response and was effective to identify high risk patients. This is potentially useful to complement current disease management.

This article offers supplementary material which is provided at the end of the article.

Keywords: colorectal cancer; KRAS; liquid biopsy; transrenal DNA

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About the article

aTao Song and Fei Mao have contributed equally to this work.


Received: 2017-07-29

Accepted: 2018-06-22

Published Online: 2018-07-17

Published in Print: 2018-12-19


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This work was supported by a research grant provided by Xiangyang No. 1 People’s Hospital.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 2, Pages 268–275, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0675.

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