Extrinsic and intrinsic preanalytical variables affecting liquid biopsy in cancer
Syeda Maheen Batool, Tiffaney Hsia, Alexandra Beecroft, Brian Lewis, Emil Ekanayake, Yulia B. Rosenfeld, A. Escobedo, Austin S. Gamblin, Siddarth Rawal, Richard J. Côté, Mark A. Watson, David T. Wong, Abhijit A. Patel, Johan Skog, Nickolas Papadopoulos, Chetan Bettegowda, Cesar M. Castro, Hakho Lee, Sudhir Srivastava, Bob S. Carter, Leonora Balaj
Abstract
Liquid biopsy, through isolation and analysis of disease-specific analytes, has evolved as a promising tool for safe and minimally invasive diagnosis and monitoring of tumors. It also has tremendous utility as a companion diagnostic allowing detection of biomarkers in a range of cancers (lung, breast, colon, ovarian, brain). However, clinical implementation and validation remains a challenge. Among other stages of development, preanalytical variables are critical in influencing the downstream cellular and molecular analysis of different analytes. Although considerable progress has been made to address these challenges, a comprehensive assessment of the impact on diagnostic parameters and consensus on standardized and optimized protocols is still lacking. Here, we summarize and critically evaluate key variables in the preanalytical stage, including study population selection, choice of biofluid, sample handling and collection, processing, and storage. There is an unmet need to develop and implement comprehensive preanalytical guidelines on the optimal practices and methodologies.