Lineage and ecology define liver tumor evolution in response to treatment
Mahler Revsine, Limin Wang, Marshonna Forgues, Shay Behrens, Amanda J. Craig, Meng Liu, Bao Tran, Michael C. Kelly, Anuradha Budhu, Cecilia Monge, Changqing Xie, Jonathan M. Hernandez, Tim F. Greten, Xin Wei Wang, Lichun Ma
Abstract
A tumor ecosystem constantly evolves over time in the face of immune predation or therapeutic intervention, resulting in treatment failure and tumor progression. Here, we present a single-cell transcriptome-based strategy to determine the evolution of longitudinal tumor biopsies from liver cancer patients by measuring cellular lineage and ecology. We construct a lineage and ecological score as joint dynamics of tumor cells and their microenvironments. Tumors may be classified into four main states in the lineage-ecological space, which are associated with clinical outcomes. Analysis of longitudinal samples reveals the evolutionary trajectory of tumors in response to treatment. We validate the lineage-ecology-based scoring system in predicting clinical outcomes using bulk transcriptomic data of additional cohorts of 716 liver cancer patients. Our study provides a framework for monitoring tumor evolution in response to therapeutic intervention.