An integrated single-cell transcriptomic dataset for non-small cell lung cancer

Prazanowska, Karolina Hanna; Lim, Su Bin

doi:10.1038/s41597-023-02074-6

Cited by 16 publications

(15 citation statements)

References 74 publications

(98 reference statements)

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“…Because pancreatic cancer is known to be the most collagen-rich cancer, we started our investigation by analyzing collagen gene expression in a publicly available single-cell RNA-seq dataset of pancreatic ductal adenocarcinoma (PDAC) patients [26]. Here, we identified subtypes of CAFs and their collagen profile, which we confirmed in a public non-small cell lung cancer (NSCLC) dataset [27]. To investigate whether these CAF-associated collagens were associated with patient outcome in PDAC and other cancers, we profiled the collagen gene expression in tumor samples from The Cancer Genome Atlas (TCGA) project [28] and evaluated the association with survival outcomes.…”

Section: Introductionmentioning

confidence: 82%

“…We used the 'FindAllMarkers' and 'FindMarkers' functions to test differential expression of collagens in the identified CAF subtypes. We analyzed NSCLC single-cell RNA-seq data from Prazanowska and Lim [27], which includes data from seven separate datasets comprising a total of 185 NSCLC tumor samples. This integrated dataset excluded cells with under 200 or over 3,000 genes per cell and cells with over 20% mitochondrial genes.…”

Section: Single-cell Rna-seq Datamentioning

confidence: 99%

“…cancer.gov/programs/cptac), and in part upon data generated by Peng and colleagues [26] (https://doi.org/10. 1038/s41422-019-0195-y), as well as data generated by Prazanowski and Lim [27] (https://doi.org/10.1038/ s41597-023-02074-6).…”

Section: Acknowledgementsmentioning

confidence: 99%

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The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

Thorlacius‐Ussing,

Jensen,

Nissen

et al. 2023

The Journal of Pathology

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Cancer‐associated fibroblasts (CAFs) deposit and remodel collagens in the tumor stroma, impacting cancer progression and efficacy of interventions. CAFs are the focus of new therapeutics with the aim of normalizing the tumor microenvironment. To do this, a better understanding of CAF heterogeneity and collagen composition in cancer is needed. In this study, we sought to profile the expression of collagens at multiple levels with the goal of identifying cancer biomarkers. We investigated the collagen expression pattern in various cell types and CAF subtypes in a publicly available single‐cell RNA sequencing (RNA‐seq) dataset of pancreatic ductal adenocarcinoma. Next, we investigated the collagen expression profile in tumor samples across cancer types from The Cancer Genome Atlas (TCGA) database and evaluated if specific patterns of collagen expression were associated with prognosis. Finally, we profiled circulating collagen peptides using a panel of immunoassays to measure collagen fragments in the serum of cancer patients. We found that pancreatic stellate cells and fibroblasts were the primary producers of collagens in the pancreas. COL1A1, COL3A1, COL5A1, COL6A1 were expressed in all CAF subtypes, whereas COL8A1, COL10A1, COL11A1, COL12A1 were specific to myofibroblast CAFs (myCAF) and COL14A1 specific to inflammatory CAFs (iCAF). In TCGA database, myCAF collagens COL10A1 and COL11A1 were elevated across solid tumor types, and multiple associations between high expression and worse survival were found. Finally, circulating collagen biomarkers were elevated in the serum of patients with cancer relative to healthy controls with COL11A1 (myCAF) having the best diagnostic accuracy of the markers measured. In conclusion, CAFs express a noncanonical collagen profile with specific collagen subtypes associated with iCAFs and myCAFs in PDAC. These collagens are deregulated at the cellular, tumor, and systemic levels across different solid tumors and associate with survival. These findings could lead to new discoveries such as novel biomarkers and therapeutic targets. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Introductionmentioning

confidence: 82%

Section: Single-cell Rna-seq Datamentioning

confidence: 99%

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The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

Thorlacius‐Ussing,

Jensen,

Nissen

et al. 2023

The Journal of Pathology

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“…However, studies on sex differences in the bladder were rarely reported, and the molecular mechanisms underlying these sex differences are not fully understood until now. In recent years, scRNA-seq has become a powerful tool to measure gene expression and explore cellular heterogeneity [ 24 ]. To explore the sex-based differences in bladder, we collected scRNA-seq data of six normal human bladders from public databases for further analysis.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection

Teng

Song

et al. 2023

BMC Med Genomics

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Background Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems. Methods We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network. Results In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes. Conclusions Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa.

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“…Single-cell RNA sequencing (scRNA-seq) data used in this study were obtained from a publicly available dataset, originally published by Karolina Hanna Prazanowska and Su Bin Lim. 27 The Seurat object of the final processed scRNA-seq dataset, including uniform manifold approximation and projection (UMAP) embeddings and precomputed cell cluster assignments, was accessed and downloaded from Figshare (https://doi.org/10.6084/m9.figsh Stromal M2-like TAM density showed a high degree of variation among the 221 LUSC TMA specimens (mean ± SD, 572.9 ± 537.4), while islet M2-like TAM density was also highly variable (mean ± SD, 158.7 ± 242.9; Figure 1C,E; Table 1). Stromal M2-like TAM density was moderately correlated with islet M2-like TAM density (r = 0.408, p < 0.0001).…”

Section: Reanalysis Of Single-cell Rna Sequencing Datamentioning

confidence: 99%

M2‐like tumor‐associated macrophages promote epithelial–mesenchymal transition through the transforming growth factor β/Smad/zinc finger e‐box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma

Sumitomo,

Menju,

Shimazu

et al. 2023

Cancer Science

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Epithelial‑mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor‐associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1‐like and M2‐like TAM distribution and EMT by E‐cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC‐1) and a human monocyte cell line (THP‐1) were used for in vitro experiments. M2‐like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E‐cadherin‐positive and 44 (19.9%) were vimentin‐positive. M2‐like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF‐β1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF‐β1 secretion from TAMs was confirmed by ELISA. TAM‐co‐cultured H226 and EBC‐1 cells exhibited EMT (decreased E‐cadherin, increased vimentin). Regarding EMT‐activating transcriptional factors, phosphorylated Smad3 and ZEB‐family proteins were higher in TAM‐co‐cultured LUSC cells than in parental cells. TAM‐co‐cultured H226 and EBC‐1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.

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An integrated single-cell transcriptomic dataset for non-small cell lung cancer

Cited by 16 publications

References 74 publications

The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection

M2‐like tumor‐associated macrophages promote epithelial–mesenchymal transition through the transforming growth factor β/Smad/zinc finger e‐box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma

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