Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer.
Biomarkers, Tumor
/ blood
Circulating Tumor DNA
/ genetics
Colonic Neoplasms
/ blood
Exosomes
/ metabolism
Female
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Liquid Biopsy
/ methods
Male
Mutation
Prognosis
Progression-Free Survival
Prospective Studies
Proto-Oncogene Proteins p21(ras)
/ blood
Rectal Neoplasms
/ blood
Rome
/ epidemiology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 11 2021
22 11 2021
Historique:
received:
10
04
2021
accepted:
14
10
2021
entrez:
23
11
2021
pubmed:
24
11
2021
medline:
9
2
2022
Statut:
epublish
Résumé
Liquid biopsy has become a useful alternative in metastatic colorectal cancer (mCRC) patients when tissue biopsy of metastatic sites is not feasible. In this study we aimed to investigate the clinical utility of circulating exosomes DNA in the management of mCRC patients. Exosomes level and KRAS mutational status in exosomal DNA was assesed in 70 mCRC patients and 29 CRC primary tumor and were analysed at different disease steps evaluating serial blood samples (240 blood samples). There was a significant correlation between the extension of disease and exosomes level and the resection of primary localized tumor was correlated with a decrease of KRAS G12V/ D copies and fractional abundance in metastatic disease. CEA expression and liver metastasis correlated with a higher number of KRAS G12V/D copies/ml and a higher fractional abundance; in the subgroup of mCRC patients eligible for surgery, the size of tumor and the radiological response were related to exosomes level but only the size was related to the number of KRAS WT copies; both KRAS wild-type and mutated levels were identified as a prognostic factor related to OS. Finally, we found that 91% of mutated mCRC patients became wild type after the first line chemotherapy but this status reverted in mutated one at progression in 80% of cases. In a prospective cohort of mCRC patients, we show how longitudinal monitoring using exosome-based liquid biopsy provides clinical information relevant to therapeutic stratification.
Identifiants
pubmed: 34811396
doi: 10.1038/s41598-021-01668-7
pii: 10.1038/s41598-021-01668-7
pmc: PMC8608842
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22686Subventions
Organisme : PRIN
ID : 2017AHTCK7 (LS7)
Informations de copyright
© 2021. The Author(s).
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