Single-cell transcriptomic analysis uncovers intratumoral heterogeneity and drug-tolerant persister in ALK-rearranged lung adenocarcinoma

Abstract

Abbreviations ADCs Adenocarcinomas ALDH1A1 Aldehyde dehydrogenase 1 family member A1 ALK Anaplastic lymphoma kinase CSC Cancer stem cell CCL20 Chemokine (C-C motif) ligand 20 CCR6 chemokine receptor 6 DGE Differential gene expression DTP Drug-tolerant persister EGFR Epidermal growth factor receptor EML4 Echinoderm microtubule-associated protein-like 4 ELISA Enzyme-linked immunosorbent assay FOS Fos Proto-Oncogene NANOG Homeobox protein NANOG ICAM-1 Intercellular adhesion molecule 1 IL-17 Interleukin-17 LCOs Lung cancer organoids MUC5AC Mucin-5AC NSCLC Non-small cell lung carcinoma POU5F1 POU Class 5 Homeobox 1 PROM1 Prominin 1 PTGS2 Prostaglandin-endoperoxide synthase 2 RORɣ Retinoid-related orphan receptor-γ S100A9 S100 calcium-binding protein A9 scRNA-seq Single-cell RNA sequencing TCGA-LUAD The Cancer Genome Atlas Lung Adenocarcinoma Th17 T helper-17 lymphocytes TKIs Tyrosine kinase inhibitors TNF Tumor necrosis factor UMI Unique molecular index UMAP Uniform Manifold Approximation and Projection Dear Editor, Non-small cell lung carcinoma (NSCLC) accounts for more than 85% of all lung cancers [ 1]. Differential gene expression (DGE) analysis of drug-resistant and drug-sensitive TS485T-O LCOs revealed that the interleukin-17 (IL-17) signaling pathway was enriched in both crizotinib-resistant and alectinib-resistant tumor organoids ( Supplementary Figure S2C-D). [...]we found that the actin cytoskeleton regulatory pathway was downregulated in both FA34-O crizotinib-resistant and alectinib-resistant tumor organoids ( Supplementary Figure S2E-F). Abbreviations: Anterior gradient 2 (AGR2); Chemokine (C-C motif) ligand 20 (CCL20); BPI fold containing family A, member 1 (BPIFA1); Cancer susceptibility candidate 1 (CASC1); Cell division cycle 20B (CDC20B); Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6); Cilia and flagella associated protein 126 (CFAP126); Coiled-Coil Domain Containing 170 (CCDC170); Coronin 2A (CORO2A); C-X-C motif chemokine ligand 8 (CXCL8); Dynein axonemal assembly factor 1 (DNAAF1); Dynein axonemal heavy chain 7 (DNAH7); EF-hand domain family member B (EFHB); Ferritin heavy chain 1 (FTH1); GINS complex subunit (GINS1); Hypoxia-inducible factors (HIF); Leucine Rich Repeat Containing 46 (LRRC46); Matrix metallopeptidase 1 (MMP1); Meiosis specific nuclear structural 1 (MNS1); Nicotinamide phosphoribosyltransferase (NAMPT); Nucleotide oligomerization domain (NOD); Myocardial infarction associated transcript (MIAT); Paternally Expressed 10 (PEG10); PIH1 domain containing 3 (PIH1D3); Primary cilia formation (PIFO); Prosaposin (PSAP); Ras-proximate-1 (RAP1); Radial spoke head component 1 (RSPH1); Regulator of cell cycle (RGCC); Rho family GTPase 1 (RND1); Rhophilin associated tail protein 1 like (ROPN1L); Ribosomal Protein L10 (RPL10); Insulin like growth factor binding protein 5 (IGFBP5); Intercellular adhesion molecule 1 (ICAM-1); Interleukin-17 (IL-17); S100 Calcium Binding Protein A9 (S100A9); Trefoil factor 1 (TFF-1); Tetraspanin 1 (TSPAN1); Threonine tyrosine kinase (TTK); T helper-17 lymphocytes (Th17); WAP four-disulfide core domain protein 2 (WFDC2) CCL20, mainly produced by mucosal lymphoid tissues, is a chemokine that directs lymphocyte migration toward epithelial cells.