Single‐cell landscape of malignant ascites from patients with metastatic colorectal cancer

Abstract

The presence of malignant ascites in colorectal cancer (CRC) patients is associated with a poor prognosis, a high risk of recurrence, and resistance to chemotherapy and immune therapy [1][2][3]. Understanding the complex interactions among different kinds of cells and the ecosystem of peritoneal metastasized colorectal cancer (pmCRC) ascites may provide insights into effective treatment strategies.We profiled the single-cell transcriptomes of 96,065 cells from ascites samples of 12 treatment-naïve patients with pmCRC using the 10× single-cell RNA-sequencing (scRNA-seq) (Supplementary Figure S1A, Supplementary Table S1). Eleven major cell types were identified by characteristic canonical cell markers, including epithelial cells, endothelial cells, fibroblasts, T cells, B cells, monocytes, macrophages, plasma cells, natural killer (NK) cells, dendritic cells (DCs), and mast cells (Figure 1A-B). The main cellular components of pmCRC ascites are T cells (40,095; 41.7%), macrophages (28,487; 29.7%), and fibroblasts (5,932; 6.2%). Compared with primary CRC, which showed 14.8% epithelial cells [4], only 0.3% (291) epithelial cells were found in the ascites. The low percentage of epithelial cells in pmCRC ascites was consistent with the scRNA-seq studies of another tumor ascites [5][6][7].We classified the 12 patients into 2 groups according to their treatment response as follows: 8 patients (P02, P03, P04, P07, P08, P09, P11, and P12) had stable disease (SD), while 4 (P01, P05, P06, and P10) had progressive disease (PD). Single-cell transcriptomic analyses have revealed high heterogeneity of cell composition in 12 patients. The SD group exhibited a higher proportion of fibroblasts and epithelial cells (Figure 1B). Remarkably, fibroblasts had significantly different expression characteristics between the 2 groups (Figure 1C), and the top five upregulated/downregulated genes were visualized in 11 cell types (Figure 1D). We also found a significant increase in the frequency of macrophages in pmCRC ascites compared with the primary tumors [4] (Figure 1E). It hinted that significant inter-patient variability in theThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.