Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer

Abstract 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...

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Autores principales:	Donatella Lucchetti, Ina Valeria Zurlo, Filomena Colella, Claudio Ricciardi-Tenore, Mariantonietta Di Salvatore, Giampaolo Tortora, Ruggero De Maria, Felice Giuliante, Alessandra Cassano, Michele Basso, Antonio Crucitti, Ilaria Laurenzana, Giulia Artemi, Alessandro Sgambato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76b8a6a6c9ab48f3a5d635c255f279da
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spelling	oai:doaj.org-article:76b8a6a6c9ab48f3a5d635c255f279da2021-11-28T12:18:16ZMutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer10.1038/s41598-021-01668-72045-2322https://doaj.org/article/76b8a6a6c9ab48f3a5d635c255f279da2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01668-7https://doaj.org/toc/2045-2322Abstract 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.Donatella LucchettiIna Valeria ZurloFilomena ColellaClaudio Ricciardi-TenoreMariantonietta Di SalvatoreGiampaolo TortoraRuggero De MariaFelice GiulianteAlessandra CassanoMichele BassoAntonio CrucittiIlaria LaurenzanaGiulia ArtemiAlessandro SgambatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Donatella Lucchetti Ina Valeria Zurlo Filomena Colella Claudio Ricciardi-Tenore Mariantonietta Di Salvatore Giampaolo Tortora Ruggero De Maria Felice Giuliante Alessandra Cassano Michele Basso Antonio Crucitti Ilaria Laurenzana Giulia Artemi Alessandro Sgambato Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
description	Abstract 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.
format	article
author	Donatella Lucchetti Ina Valeria Zurlo Filomena Colella Claudio Ricciardi-Tenore Mariantonietta Di Salvatore Giampaolo Tortora Ruggero De Maria Felice Giuliante Alessandra Cassano Michele Basso Antonio Crucitti Ilaria Laurenzana Giulia Artemi Alessandro Sgambato
author_facet	Donatella Lucchetti Ina Valeria Zurlo Filomena Colella Claudio Ricciardi-Tenore Mariantonietta Di Salvatore Giampaolo Tortora Ruggero De Maria Felice Giuliante Alessandra Cassano Michele Basso Antonio Crucitti Ilaria Laurenzana Giulia Artemi Alessandro Sgambato
author_sort	Donatella Lucchetti
title	Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
title_short	Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
title_full	Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
title_fullStr	Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
title_full_unstemmed	Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
title_sort	mutational status of plasma exosomal kras predicts outcome in patients with metastatic colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/76b8a6a6c9ab48f3a5d635c255f279da
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Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer

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