Liquid Biopsy-Based Single-Cell Transcriptome Profiling Characterizes Heterogeneity of Disseminated Tumor Cells from Lung Adenocarcinoma.

The advent of rapid and inexpensive sequencing technology allows scientists to decipher intratumor heterogeneity spatially and temporally for resolving the evolutionary history of tumor and the underlying mechanism. However, studies on characterizing heterogeneity of disseminated tumor cells (DTCs) in liquid biopsies are rare because of the rarity and low viability of DTCs as well as a large number non-tumor cells. Here, we employed high-throughput single-cell transcriptome sequencing technology and rare DTC enrichment method to decipher the heterogeneity and distinct molecular signatures of DTCs in malignant pleural effusion (MPE) from lung adenocarcinoma. Single-cell transcriptomes of 8,213 MPE-derived cells were acquired for bioinformatics analysis. In these cells from MPE, five main cell populations including tumor, mesothelial, monocyte, T and B cells were identified with specific markers for each group. Tumor cells present in MPE were further divided into four distinct subgroups that were found to be associated with immune response, cell proliferation, apoptosis and cell adhesion, respectively. Based on the single-cell dataset of MPE-derived DTCs, we identified 19 tumor-specific markers that were also highly expressed at RNA and protein levels in tumor tissues as candidate markers for detection of extraordinarily rare circulating tumor cells in the blood. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.