TY - JOUR
T1 - A distinctive microrna (Mirna) signature in the blood of colorectal cancer (crc) patients at surgery
AU - Gasparello, Jessica
AU - Papi, Chiara
AU - Allegretti, Matteo
AU - Giordani, Elena
AU - Carboni, Fabio
AU - Zazza, Settimio
AU - Pescarmona, Edoardo
AU - Romania, Paolo
AU - Giacomini, Patrizio
AU - Scapoli, Chiara
AU - Gambari, Roberto
AU - Finotti, Alessia
N1 - Funding Information:
Funding: This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG #13575 to RG; IG #19052 to PG; Nuvenia Fellowship ID#19503 to MA). This study was also supported by the European Union (EU) Horizon 2020 Research and Innovation Programme (GA #633937, project ULTRAsensitive PLAsmonic devices for early CAncer Diagnosis (ULTRAPLACAD)) and by the Interuniversity Consortium for the Biotechnology, Italy.
Funding Information:
This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG #13575 to RG; IG #19052 to PG; Nuvenia Fellowship ID#19503 to MA). This study was also supported by the European Union (EU) Horizon 2020 Research and Innovation Programme (GA #633937, project ULTRAsensitive PLAsmonic devices for early CAncer Diagnosis (ULTRAPLACAD)) and by the Interuniversity Consortium for the Biotechnology, Italy. Acknowledgments: The authors are grateful to Cristian Bassi PhD (LTTA: Laboratorio per le Tecnologie delle Terapie Avanzate, Microarray Facility, University of Ferrara) for bioinformatic analysis support.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - Background: Liquid biopsy (LB) provides an examination of the peripheral blood of cancer patients for circulating tumor cells, cell-free nucleic acids and microRNAs (miRNAs) and is an established tool of precision medicine. Unlike most previous LB studies that focused on advanced metastatic colorectal cancer (CRC), we assessed miRNA dysregulation in blood samples obtained on the day of surgery from patients with primary CRC lesions but no clinical evidence of extra-colonic diffusion. In this study, plasma preparation included miRNAs associated to exosomes, but excluded large macrovesicles from the preparation. Methods: The miRNA profile in plasma isolated from a cohort of 35 CRC patients at the day of surgery was analyzed by Next Generation Sequencing (NGS) and further confirmed by droplet digital RT-PCR (dd-RT-PCR). Results: A miR-141-3p/miR-221-3p/miR-222-3p upregulation signature previously described in advanced CRC did not discriminate the analyzed early-CRC cohort from six tumor-free donors (Tf-D). In contrast, NGS-based miRNome analysis of a training cohort of five CRC and three tumor-free donors identified a novel, distinct nine miRNA signature comprising five up-regulated and four down-regulated miRNAs, six of which could be confirmed in the full CRC and tumor-free donor validation dataset by dd-RT-PCR. Additionally, a KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutant status was correlated with the plasma content of three identified miRNAs. Conclusions: When the data obtained were comparatively evaluated, at least one of the miRNAs belonging to the signature list was found to be dysregulated in 34/35 (97.1%) of our early-CRC plasma samples. The miRNA list provides diagnostic markers as well as possible molecular targets for protocols focusing on “microRNA therapeutics”.
AB - Background: Liquid biopsy (LB) provides an examination of the peripheral blood of cancer patients for circulating tumor cells, cell-free nucleic acids and microRNAs (miRNAs) and is an established tool of precision medicine. Unlike most previous LB studies that focused on advanced metastatic colorectal cancer (CRC), we assessed miRNA dysregulation in blood samples obtained on the day of surgery from patients with primary CRC lesions but no clinical evidence of extra-colonic diffusion. In this study, plasma preparation included miRNAs associated to exosomes, but excluded large macrovesicles from the preparation. Methods: The miRNA profile in plasma isolated from a cohort of 35 CRC patients at the day of surgery was analyzed by Next Generation Sequencing (NGS) and further confirmed by droplet digital RT-PCR (dd-RT-PCR). Results: A miR-141-3p/miR-221-3p/miR-222-3p upregulation signature previously described in advanced CRC did not discriminate the analyzed early-CRC cohort from six tumor-free donors (Tf-D). In contrast, NGS-based miRNome analysis of a training cohort of five CRC and three tumor-free donors identified a novel, distinct nine miRNA signature comprising five up-regulated and four down-regulated miRNAs, six of which could be confirmed in the full CRC and tumor-free donor validation dataset by dd-RT-PCR. Additionally, a KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutant status was correlated with the plasma content of three identified miRNAs. Conclusions: When the data obtained were comparatively evaluated, at least one of the miRNAs belonging to the signature list was found to be dysregulated in 34/35 (97.1%) of our early-CRC plasma samples. The miRNA list provides diagnostic markers as well as possible molecular targets for protocols focusing on “microRNA therapeutics”.
KW - Circulating miRNA
KW - Colorectal cancer
KW - Droplet digital PCR
KW - Liquid biopsy
KW - Next generation sequencing
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U2 - 10.3390/cancers12092410
DO - 10.3390/cancers12092410
M3 - Article
AN - SCOPUS:85090610966
VL - 12
SP - 1
EP - 15
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 9
M1 - 2410
ER -