TY - JOUR
T1 - Development of circulating microRNA-based biomarkers for medical decision-making
T2 - a friendly reminder of what should NOT be done
AU - Lakkisto, P. ivi
AU - Dalgaard, Louise Torp
AU - On behalf of EU-CardioRNA COST Action CA17129
AU - Belmonte, Thalia
AU - Pinto-Sietsma, Sara-Joan
AU - Devaux, Yvan
AU - de Gonzalo-Calvo, David
N1 - Funding Information: This article is based upon work from EU-CardioRNA COST Action CA17129 (https://cardiorna.eu/) supported by COST (European Cooperation in Science and Technology). DdGC has received financial support from Instituto de Salud Carlos III [Miguel Servet 2020: CP20/00041], co-funded by the European Social Fund (ESF)/“Investing in your future.” This work is supported by Instituto de Salud Carlos III [PI20/00577], co-funded by European Regional Development Fund (ERDF)/“A way to make Europe.” CIBERES is an initiative of the Instituto de Salud Carlos III. YD is funded by the EU Horizon 2020 project COVIRNA (Grant Agreement # 101016072), the National Research Fund [grants # C14/BM/8225223, C17/BM/11613033, and COVID-19/2020-1/14719577/miRCOVID], the Ministry of Higher Education and Research, and the Heart Foundation-Daniel Wagner of Luxembourg. PL is funded by the Finnish Cultural Foundation, The Finnish Foundation for Cardiovascular Research, The Finnish Society of Clinical Chemistry, and the Finnish Foundation for Laboratory Medicine. We would like to thank all EU-CardioRNA COST Action members for insightful discussions that contributed to drafting the current paper. Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Circulating cell-free microRNAs (miRNAs) represent a major reservoir for biomarker discovery. Unfortunately, their implementation in clinical practice is limited due to a profound lack of reproducibility. The great technical variability linked to major pre-analytical and analytical caveats makes the interpretation of circulating cell-free miRNA data challenging and leads to inconsistent findings. Additional efforts directed to standardization are fundamental. Several well-established protocols are currently used by independent groups worldwide. Nonetheless, there are some specific aspects in specimen collection and processing, sample handling, miRNA quantification, and data analysis that should be considered to ensure reproducibility of results. Here, we have addressed this challenge using an alternative approach. We have highlighted and discussed common pitfalls that negatively impact the robustness of circulating miRNA quantification and their application for clinical decision-making. Furthermore, we provide a checklist usable by investigators to facilitate and ensure the control of the whole miRNA quantification and analytical process. We expect that these recommendations improve the reproducibility of findings, and ultimately, facilitate the incorporation of circulating miRNA profiles into clinical practice as the next generation of disease biomarkers.
AB - Circulating cell-free microRNAs (miRNAs) represent a major reservoir for biomarker discovery. Unfortunately, their implementation in clinical practice is limited due to a profound lack of reproducibility. The great technical variability linked to major pre-analytical and analytical caveats makes the interpretation of circulating cell-free miRNA data challenging and leads to inconsistent findings. Additional efforts directed to standardization are fundamental. Several well-established protocols are currently used by independent groups worldwide. Nonetheless, there are some specific aspects in specimen collection and processing, sample handling, miRNA quantification, and data analysis that should be considered to ensure reproducibility of results. Here, we have addressed this challenge using an alternative approach. We have highlighted and discussed common pitfalls that negatively impact the robustness of circulating miRNA quantification and their application for clinical decision-making. Furthermore, we provide a checklist usable by investigators to facilitate and ensure the control of the whole miRNA quantification and analytical process. We expect that these recommendations improve the reproducibility of findings, and ultimately, facilitate the incorporation of circulating miRNA profiles into clinical practice as the next generation of disease biomarkers.
KW - Biomarker
KW - limitation
KW - methodology
KW - microRNA
KW - pitfall
UR - http://www.scopus.com/inward/record.url?scp=85141411434&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/10408363.2022.2128030
DO - https://doi.org/10.1080/10408363.2022.2128030
M3 - Review article
C2 - 36325621
SN - 1040-8363
JO - Critical Reviews in Clinical Laboratory Sciences
JF - Critical Reviews in Clinical Laboratory Sciences
ER -