» Articles » PMID: 38524605

Single Cell Analyses of Cancer Cells Identified Two Regulatorily and Functionally Distinct Categories in Differentially Expressed Genes Among Tumor Subclones

Overview
Journal Heliyon
Specialty Social Sciences
Date 2024 Mar 25
PMID 38524605
Authors
Affiliations
Soon will be listed here.
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 and DEG. DEG, 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, 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 tends to involve in cell-cell contact while DEG tends to involve in secreted signaling, which further support that DEG and DEG are two regulatorily and functionally distinct categories.

References
1.
Qi J, Sun H, Zhang Y, Wang Z, Xun Z, Li Z . Single-cell and spatial analysis reveal interaction of FAP fibroblasts and SPP1 macrophages in colorectal cancer. Nat Commun. 2022; 13(1):1742. PMC: 8976074. DOI: 10.1038/s41467-022-29366-6. View

2.
Azizi E, Carr A, Plitas G, Cornish A, Konopacki C, Prabhakaran S . Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018; 174(5):1293-1308.e36. PMC: 6348010. DOI: 10.1016/j.cell.2018.05.060. View

3.
Richards L, Whitley O, MacLeod G, Cavalli F, Coutinho F, Jaramillo J . Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity. Nat Cancer. 2022; 2(2):157-173. DOI: 10.1038/s43018-020-00154-9. View

4.
Qiu X, Mao Q, Tang Y, Wang L, Chawla R, Pliner H . Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017; 14(10):979-982. PMC: 5764547. DOI: 10.1038/nmeth.4402. View

5.
Becker W, Nevins S, Chen D, Chiu R, Horning A, Guha T . Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer. Nat Genet. 2022; 54(7):985-995. PMC: 9279149. DOI: 10.1038/s41588-022-01088-x. View