Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma.

ABSTRACT: Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

SUBMITTER: Kim N

PROVIDER: S-EPMC7210975 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Single-cell RNA sequencing reveals the cellular and molecular changes that contribute to the progression of lung adenocarcinoma

Project description:Pure ground glass nodules (GGNs) and solid nodules (SNs) represent early and relatively late stages of lung adenocarcinoma (LUAD) in radiology, respectively. The cellular and molecular characteristics of pure GGNs and SNs have not been comprehensively elucidated. Additionally, the mechanism driving the progression of lung adenocarcinoma from pure GGN to SN in radiology is also elusive. In this study, by analyzing the single-cell transcriptomic profiles of 76,762 cells from four pure GGNs, four SNs, and four normal tissues, we found that anti-tumor immunity mediated by NK and CD8+T cells gradually weakened with the progression of LUAD and humoral immunity mediated by plasma B cells was more active in SNs. Additionally, the proliferation ability of some special epithelial cell increased during the progression process from pure GGN to SN. Furthermore, stromal cells and M2 macrophages could assist the progression of LUAD. Through comprehensive analyses, we revealed dynamic changes in cellular components and intercellular interactions during the progression of LUAD. These findings could facilitate our understanding of LUAD and discovery of novel therapeutic targets.

| S-EPMC9420948 | biostudies-literature

Single-Cell RNA Sequencing of Metastatic Testicular Seminoma Reveals the Cellular and Molecular Characteristics of Metastatic Cell Lineage.

Project description:BackgroundTesticular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumors, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying.MethodsWe performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumor tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumor cell subtypes at the scRNA level.ResultsA single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumor cells in testicular seminoma, especially metastatic tumor cells. KRT8 and KRT18 were commonly expressed in the three tumor cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumor cell subtypes in primary tumor sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified.ConclusionsWe revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumor cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.

| S-EPMC9039315 | biostudies-literature

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

Project description: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.

| S-EPMC7695431 | biostudies-literature

Single-cell RNA sequencing analysis revealed cellular and molecular immune profiles in lung squamous cell carcinoma.

Project description:Although breakthroughs have been made in the treatment of non-small cell lung cancer, there are only a few choices for advanced-stage or recurrent lung squamous cell carcinoma (LUSC) patients. In our study, we identified 7 major cell types in thedepicted the immunolandscape of LUSC microenvironment using single-cell RNA sequencing. We found that an immunosuppressive receptor, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), was highly expressed by regulatory T cells (Tregs) and exhausted CD8+T cells, suggesting that upregulation of TIGIT might promote an immunosuppressive microenvironment and inhibit the cytotoxic ability of CD8+T cells. We also identified tumor-associated neutrophil (TAN), characterized by CXCR2, CSF3R and CXCL8, in the tumor region, and TANs upregulated the expression of interleukin 1 receptor antagonist (IL1RN) which suggested that TAN might exert an immunosuppressive role via expressing IL1RN. Furthermore, the number of SPP1+ macrophages(SPP1+M) significantly increased in tumor microenvirnment, which was correlated with the poor survival of patients. Additionally, regulatory networks based on SPP1+M revealed that the disparities of several ligand-receptor pairs existed between tumor and normal tissues. Among these pairs, SPP1-CD44 showed the most interactions between SPP1+M and other cell types. Our results provided deep insight into the immune landscape of LUSC and an essential resource for drug discovery in the future.

| S-EPMC9586982 | biostudies-literature

Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of gliomas and lung cancer brain metastases.

Project description:BackgroundBrain malignancies encompass gliomas and brain metastases originating from extracranial tumours including lung cancer. Approximately 50% of patients with lung adenocarcinoma (LUAD) will eventually develop brain metastases. However, the specific characteristics of gliomas and lung-to-brain metastases (LC) are largely unknown.MethodsWe applied single-cell RNA sequencing to profile immune and nonimmune cells in 4 glioma and 10 LC samples.ResultsOur analysis revealed that tumour microenvironment (TME) cells are present in heterogeneous subpopulations. LC reprogramed cells into immune suppressed state, including microglia, macrophages, endothelial cells, and CD8+ T cells, with unique cell proportions and gene signatures. Particularly, we identified that a subset of macrophages was associated with poor prognosis. ROS (reactive oxygen species)-producing neutrophils was found to participant in angiogenesis. Furthermore, endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited high heterogeneity in chromosomal instability (CIN) and cell population.ConclusionsOur findings provide a comprehensive understanding of the heterogenicity of the tumor microenvironment and tumour cells and it will be crucial for successful immunotherapy development for brain metastasis of lung cancer.

| S-EPMC9637666 | biostudies-literature

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma.

Project description:Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues. Our analyses revealed heterogeneous carcinoma cell transcriptomes reflecting histological grade and oncogenic pathway activities, and two distinct microenvironmental patterns. The immune-activated CP²E microenvironment was composed of cancer-associated myofibroblasts, proinflammatory monocyte-derived macrophages, plasmacytoid dendritic cells and exhausted CD8+ T cells, and was prognostically unfavorable. In contrast, the inert N³MC microenvironment was characterized by normal-like myofibroblasts, non-inflammatory monocyte-derived macrophages, NK cells, myeloid dendritic cells and conventional T cells, and was associated with a favorable prognosis. Microenvironmental marker genes and signatures identified in single-cell profiles had progonostic value in bulk tumor profiles. In summary, single-cell RNA profiling of lung adenocarcinoma provides additional prognostic information based on the microenvironment, and may help to predict therapy response and to reveal possible target cell populations for future therapeutic approaches.

| S-EPMC8677623 | biostudies-literature

Resolving the Spatial and Cellular Architecture of Lung Adenocarcinoma by Multiregion Single-Cell Sequencing.

Project description:Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand-receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment. SIGNIFICANCE: The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.This article is highlighted in the In This Issue feature, p. 2355.

| S-EPMC8487926 | biostudies-literature

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing.

Project description:Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.

| S-EPMC8586023 | biostudies-literature

Mapping Cellular Reprogramming via Pooled Overexpression Screens with Paired Fitness and Single-Cell RNA-Sequencing Readout.

Project description:Understanding the effects of genetic perturbations on the cellular state has been challenging using traditional pooled screens, which typically rely on the delivery of a single perturbation per cell and unidimensional phenotypic readouts. Here, we use barcoded open reading frame overexpression libraries coupled with single-cell RNA sequencing to assay cell state and fitness, a technique we call SEUSS (scalable functional screening by sequencing). Using SEUSS, we perturbed hPSCs with a library of developmentally critical transcription factors (TFs) and assayed the impact of TF overexpression on fitness and transcriptomic states. We further leveraged the versatility of the ORF library approach to assay mutant genes and whole gene families. From the transcriptomic responses, we built genetic co-regulatory networks to identify altered gene modules and found that KLF4 and SNAI2 drive opposing effects along the epithelial-mesenchymal transition axis. From the fitness responses, we identified ETV2 as a driver of reprogramming toward an endothelial-like state.

| S-EPMC6311450 | biostudies-literature

Single-cell RNA sequencing of lung adenocarcinoma reveals heterogeneity of immune response-related genes.

Project description:Immunotherapy has emerged as a promising approach to treat cancer. However, partial responses across multiple clinical trials support the significance of characterizing intertumor and intratumor heterogeneity to achieve better clinical results and as potential tools in selecting patients for different types of cancer immunotherapies. Yet, the type of heterogeneity that informs clinical outcome and patient selection has not been fully explored. In particular, the lack of characterization of immune response-related genes in cancer cells hinders the further development of metrics to select and optimize immunotherapy. Therefore, we analyzed single-cell RNA-Seq data from lung adenocarcinoma patients and cell lines to characterize the intratumor heterogeneity of immune response-related genes and demonstrated their potential impact on the efficacy of immunotherapy. We discovered that IFN-γ signaling pathway genes are heterogeneously expressed and coregulated with other genes in single cancer cells, including MHC class II (MHCII) genes. The downregulation of genes in IFN-γ signaling pathways in cell lines corresponds to an acquired resistance phenotype. Moreover, analysis of 2 groups of tumor-restricted antigens, namely neoantigens and cancer testis antigens, revealed heterogeneity in their expression in single cells. These analyses provide a rationale for applying multiantigen combinatorial therapies to prevent tumor escape and establish a basis for future development of prognostic metrics based on intratumor heterogeneity.

| S-EPMC6478414 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data