Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones

Wei Cao; Xuefei Wang; Kaiwen Luo; Yang Li; Jiahong Sun; Ruqing Fu; Qi Zhang; Ni Hong; Edwin Cheung; Wenfei Jin

doi:10.1016/j.heliyon.2024.e28071

Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones

Heliyon. 2024 Mar 12;10(6):e28071. doi: 10.1016/j.heliyon.2024.e28071. eCollection 2024 Mar 30.

Authors

Wei Cao^{1

2}, Xuefei Wang¹, Kaiwen Luo¹, Yang Li³, Jiahong Sun¹, Ruqing Fu¹, Qi Zhang¹, Ni Hong¹, Edwin Cheung², Wenfei Jin⁴

Affiliations

¹ School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
² Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR.
³ Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.
⁴ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

To explore the feature of cancer cells and tumor subclones, we analyzed 101,065 single-cell transcriptomes from 12 colorectal cancer (CRC) patients and 92 single cell genomes from one of these patients. We found cancer cells, endothelial cells and stromal cells in tumor tissue expressed much more genes and had stronger cell-cell interactions than their counterparts in normal tissue. We identified copy number variations (CNVs) in each cancer cell and found correlation between gene copy number and expression level in cancer cells at single cell resolution. Analysis of tumor subclones inferred by CNVs showed accumulation of mutations in each tumor subclone along lineage trajectories. We found differentially expressed genes (DEGs) between tumor subclones had two populations: DEG_CNV and DEG_reg. DEG_CNV, showing high CNV-expression correlation and whose expression differences depend on the differences of CNV level, enriched in housekeeping genes and cell adhesion associated genes. DEG_reg, showing low CNV-expression correlation and mainly in low CNV variation regions and regions without CNVs, enriched in cytokine signaling genes. Furthermore, cell-cell communication analyses showed that DEG_CNV tends to involve in cell-cell contact while DEG_reg tends to involve in secreted signaling, which further support that DEG_CNV and DEG_reg are two regulatorily and functionally distinct categories.

Keywords: Cell-cell communication; Colorectal cancer; Copy number variations; Differentially expressed gene; Single cell RNA sequencing; Single cell whole genome sequencing.