Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma

Abstract

In this study, we performed single-cell transcriptome data analysis of fifty primary and metastatic lung adenocarcinoma (LUAD) samples from the GSE123902 and GSE131907 datasets to determine the landscape of inter-patient and intra-tumoral heterogeneity. The gene expression profiles and copy number variations (CNV) showed significant heterogeneity in the primary and metastatic LUAD samples. We observed upregulation of pathways related to translational initiation, endoplasmic reticulum stress, exosomes, and unfolded protein response in the brain metastasis samples as compared to the primary tumor samples. Pathways related to exosomes, cell adhesion and metabolism were upregulated and the epithelial-to-mesenchymal-transition (EMT) pathway was downregulated in brain metastasis samples from chemotherapy-treated LUAD patients as compared to those from the untreated LUAD patients. Tumor cell subgroups in the brain metastasis samples showed differential expression of genes related to type II alveolar cells, chemoresistance, glycolysis and oxidative phosphorylation (metabolic reprogramming), and EMT. Thus, single-cell transcriptome analysis demonstrated intra-patient and intra-tumor heterogeneity in the regulation of pathways related to tumor progression, chemoresistance and metabolism in the primary and metastatic LUAD tissues. Moreover, our study demonstrates that single cell transcriptome analysis is a potentially useful tool for accurate diagnosis and personalized targeted treatment of LUAD patients.