TY - JOUR
T1 - Urinary volatile organic compounds for colorectal cancer screening
T2 - A systematic review and meta-analysis
AU - van Liere, Elsa L. S. A.
AU - van Dijk, Laura J.
AU - Bosch, Sofie
AU - Vermeulen, Louis
AU - Heymans, Martijn W.
AU - Burchell, George L.
AU - de Meij, Tim G. J.
AU - Ramsoekh, Dewkoemar
AU - de Boer, Nanne K. H.
N1 - Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EvL, LvD, MH, GB and SB have nothing to declare. LV received consultancy fees from Bayer, MSD, Genentech, Servier, and Pierre Fabre, but these had no relation to the content of this publication. LV is a New York Stem Cell Foundation–Robertson Investigator. NdB has served as a speaker for AbbVie and MSD and has served as a consultant and principal investigator for TEVA Pharma BV and Takeda. He has received a research grant (unrestricted) from Dr. Falk, TEVA Pharma BV, Dutch Digestive Foundation (MLDS) and Takeda; all outside the submitted work. TdM has served as a speaker for Nutricia, Mead Johnson and Winclove. He has served as an advisory board member for Nutricia. DR has received a research grant (unrestricted) from AbbVie, outside the submitted work. He has served as a member of the Data Safety Monitoring Board of Vivoryon Therapeutics. Funding Information: This study was funded by Dutch Digestive Foundation (MLDS). The funding organisation did not have any involvement in the study’s design, conduct or reporting. Publisher Copyright: © 2023 The Author(s)
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Background: The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia. Methods: A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database. Results: Sixteen studies—involving 837 CRC patients and 1618 controls—were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73–91%) and 70% (95% CI 63–77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied. Conclusion: Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
AB - Background: The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia. Methods: A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database. Results: Sixteen studies—involving 837 CRC patients and 1618 controls—were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73–91%) and 70% (95% CI 63–77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied. Conclusion: Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
KW - Adenomas
KW - Biomarkers
KW - Colorectal cancer
KW - Electronic nose
KW - Screening
KW - Volatile organic compounds
UR - http://www.scopus.com/inward/record.url?scp=85151691927&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85151691927&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/37030079
U2 - https://doi.org/10.1016/j.ejca.2023.03.002
DO - https://doi.org/10.1016/j.ejca.2023.03.002
M3 - Review article
C2 - 37030079
SN - 0959-8049
VL - 186
SP - 69
EP - 82
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -