TY - JOUR
T1 - Liquid Biopsies for Colorectal Cancer and Advanced Adenoma Screening and Surveillance
T2 - What to Measure?
AU - Eikenboom, Ellis L.
AU - Wilting, Saskia M.
AU - Deger, Teoman
AU - Srebniak, Malgorzata I.
AU - Van Veghel-Plandsoen, Monique
AU - Boers, Ruben G.
AU - Boers, Joachim B.
AU - van IJcken, Wilfred F.J.
AU - Gribnau, Joost H.
AU - Atmodimedjo, Peggy
AU - Dubbink, Hendrikus J.
AU - Martens, John W.M.
AU - Spaander, Manon C.W.
AU - Wagner, Anja
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/9/17
Y1 - 2023/9/17
N2 - Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. In this prospective, proof-of-concept study, patients with colonoscopies for Lynch surveillance or the National Colorectal Cancer screening program were included between 7 July 2019 and 3 June 2022. Blood was drawn, and if advanced neoplasia (adenoma with villous component, high-grade dysplasia, ≥10 mm, or CRC) was detected, it was analyzed for chromosomal copy number variations, single nucleotide variants, and genome-wide methylation (MeD-seq). Outcomes were compared with corresponding patients’ tissues and the MeD-seq results of healthy blood donors. Two Lynch carriers and eight screening program patients were included: five with CRC and five with advanced adenomas. cfDNA showed copy number variations and single nucleotide variants in one patient with CRC and liver metastases. Eight patients analyzed with MeD-seq showed clustering of Lynch-associated and sporadic microsatellite instable lesions separate from microsatellite stable lesions, as did healthy blood donors. In conclusion, whereas copy number changes and single nucleotide variants were only detected in one patient, cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, rendering this tool particularly promising for LS surveillance. Larger studies are warranted to validate these findings.
AB - Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. In this prospective, proof-of-concept study, patients with colonoscopies for Lynch surveillance or the National Colorectal Cancer screening program were included between 7 July 2019 and 3 June 2022. Blood was drawn, and if advanced neoplasia (adenoma with villous component, high-grade dysplasia, ≥10 mm, or CRC) was detected, it was analyzed for chromosomal copy number variations, single nucleotide variants, and genome-wide methylation (MeD-seq). Outcomes were compared with corresponding patients’ tissues and the MeD-seq results of healthy blood donors. Two Lynch carriers and eight screening program patients were included: five with CRC and five with advanced adenomas. cfDNA showed copy number variations and single nucleotide variants in one patient with CRC and liver metastases. Eight patients analyzed with MeD-seq showed clustering of Lynch-associated and sporadic microsatellite instable lesions separate from microsatellite stable lesions, as did healthy blood donors. In conclusion, whereas copy number changes and single nucleotide variants were only detected in one patient, cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, rendering this tool particularly promising for LS surveillance. Larger studies are warranted to validate these findings.
UR - http://www.scopus.com/inward/record.url?scp=85172759282&partnerID=8YFLogxK
U2 - 10.3390/cancers15184607
DO - 10.3390/cancers15184607
M3 - Article
C2 - 37760576
AN - SCOPUS:85172759282
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 18
M1 - 4607
ER -
