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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-01668-7 |
| _version_ | 1818992099480043520 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T20:20:47Z |
| format | Article |
| id | doaj.art-76b8a6a6c9ab48f3a5d635c255f279da |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:20:47Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-76b8a6a6c9ab48f3a5d635c255f279da2022-12-21T19:27:35ZengNature PortfolioScientific Reports2045-23222021-11-0111111410.1038/s41598-021-01668-7Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancerDonatella Lucchetti0Ina Valeria Zurlo1Filomena Colella2Claudio Ricciardi-Tenore3Mariantonietta Di Salvatore4Giampaolo Tortora5Ruggero De Maria6Felice Giuliante7Alessandra Cassano8Michele Basso9Antonio Crucitti10Ilaria Laurenzana11Giulia Artemi12Alessandro Sgambato13Department of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCSDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCSDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCSDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreCentro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB)Department of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro CuoreAbstract 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.https://doi.org/10.1038/s41598-021-01668-7 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-01668-7 |
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