E3aa8956-bde8-431b-b5a5-49730710f586 - samples
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ABSTRACT:
PROVIDER: EGAD00001006457 | EGA |
REPOSITORIES: EGA
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Project description:The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.
| EGAS00001004754 | EGA
Project description:Lung adenocarcinoma is the most common histological subtype of lung cancer. Although early-stage LUAD (esLUAD) patients have much better prognosis than patients with advanced disease, among early stage patients treated primarily with surgery, some of early stage patients will develop metastasis with overall 5 year survival for stage 1 and 2 non-small cell lung cancer of 70% and 35%, respectively. Within lung adenocarcinoma, histology is heterogenous and associated with tumor invasion and clinical outcomes. Invasiveness is one of cancer hallmarks and is directly related with metastatic potential and clinical outcomes of the tumor. In this study, we characterize invasiveness mechanisms in esLUAD by analyzing gene expression of a novel cohort of 53 histologically heterogenous esLUAD samples.
2022-02-01 | GSE166720 | GEO
Project description:Background: Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods: we integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results: Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions: Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.
2023-11-25 | GSE233774 | GEO
Project description:To illuminate the evolutionary trajectory of LUAD from AIS to IAC, high-throughput scRNA-seq and ST data were generated and integrated to create a large-scale, single-cell spatiotemporal atlas of LUAD. We compiled a multi-omics atlas of the early-stage LUAD invasion process that reflects the heterogeneity of cancer cells, the competitive polyclonal origin of LUAD, signalling interactions between cancer cells and the TME, and the pseudo-chronological nature of LUAD invasion. The spatial distribution characteristics of LUAD cells revealed the spatial heterogeneity of LUAD and the mechanism of spatial immune escape in LUAD, which provides strong evidence supporting clinical diagnosis and surgical intervention at the single-cell level.
2021-11-30 | GSE189357 | GEO
Project description:To identification of key drivers involved in the development of muscle invasive bladder cancer, which displays poor prognosis, we isolated one subpopulation of human 5637 bladder cancer cells with highly invasiveness and the other subpopulation of 5637 cells with low invasiveness by Transwell method. Through proteomic analysis, differentially expressed proteins were displayed.
2018-08-27 | MSV000082854 | MassIVE
Project description:To illuminate the evolutionary trajectory of LUAD from AIS to IAC, high-throughput scRNA-seq and ST data were generated and integrated to create a large-scale, single-cell spatiotemporal atlas of LUAD. We compiled a multi-omics atlas of the early-stage LUAD invasion process that reflects the heterogeneity of cancer cells, the competitive polyclonal origin of LUAD, signalling interactions between cancer cells and the TME, and the pseudo-chronological nature of LUAD invasion. The spatial distribution characteristics of LUAD cells revealed the spatial heterogeneity of LUAD and the mechanism of spatial immune escape in LUAD, which provides strong evidence supporting clinical diagnosis and surgical intervention at the single-cell level. The seurat object of ST data are available on https://drive.google.com/drive/folders/1dkGF4kKMbHSm04DKHg6P_y_iTD1pXCH8?usp=sharing.
2021-11-30 | GSE189487 | GEO
Project description:The cell ecology and spatial niche implicated in the dynamic and sequential process of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) have not yet been elucidated. Here, we performed an integrative analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to characterize the cell atlas of the invasion trajectory of LUAD. We found that the UBE2C + cancer cell subpopulation constantly increased during the invasive process of LUAD with remarkable elevation in IAC, and its spatial distribution was in the peripheral cancer region of the IAC, representing a more malignant phenotype. Furthermore, analysis of the TME cell type subpopulation showed a constant decrease in mast cells, monocytes, and lymphatic endothelial cells, which were implicated in the whole process of invasive LUAD, accompanied by an increase in NK cells and MALT B cells from AIS to MIA and an increase in Tregs and secretory B cells from MIA to IAC. Notably, for AIS, cancer cells, NK cells, and mast cells were colocalized in the cancer region; however, for IAC, Tregs colocalized with cancer cells. Finally, communication and interaction between cancer cells and TME cell-induced constitutive activation of TGF-β signaling were involved in the invasion of IAC. Therefore, our results reveal the specific cellular information and spatial architecture of cancer cells and TME subpopulations, as well as the cellular interaction between them, which will facilitate the identification and development of precision medicine in the invasive process of LUAD from AIS to IAC.
2024-11-26 | GSE282617 | GEO
Project description:Invasive subtypes of lung adenocarcinoma (LUAD) show MDM2 amplification that is associated with poor survival. Mouse double minute 2 (MDM2) is frequently amplified in lung adenocarcinoma (LUAD) and is a negative regulator of p53, which binds to p53 and regulates its activity and stability. Genomic amplification and overexpression of MDM2 together with genetic alterations in p53 leads to genomic and genetic heterogeneity in LUAD that represents a therapeutic target. In vitro assays in a panel of LUAD cell lines showed that tumor cell response to MDM2 targeted therapy is associated with MDM2 amplification.
2022-12-31 | GSE191171 | GEO
Project description:One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, the nature of the invasiveness remains poorly characterized. Here, we established a highly invasive glioma cell line (U87R4 cells) and a non-invasive cell line (U87L4 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation. Compared to U87L4 cells, U87R4 cells were highly invasive and had glioma stem cell-like properties. Microarray analysis showed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated, whereas several cancer stem cell-relevant genes (Wnt10A, Frizzled 4, and CD44) were upregulated in U87R4 cells compared to U87L4 cells. U87R4 cells were resistant to anticancer drug-induced cell death, which was partially due to downregulation of caspase3 and PDCD4. U87R4 cells retained activated Wnt/β-catenin signaling through Frizzled 4, which was sufficient to control neurosphere formation. In addition, Frizzled 4 promoted expression of the epithelial to mesenchymal transition regulator, SNAI1, and acquisition of a mesenchymal phenotype. Taken together, our results indicate that Frizzled 4 may be a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and may be a major cause of GBM recurrence and poor prognosis. We established a highly invasive glioma cell line (U87R4 cells) and a non-invasive cell line (U87L4 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation to characterize the mRNA expression profile of highly invasive glioma cells compared to non-invasive/parental glioma cell lines.
2010-05-27 | E-GEOD-21570 | biostudies-arrayexpress
Project description:Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Understanding the dysregulated epigenetics governing LUAD progression is pivotal for identifying therapeutic targets. CBX4, a chromobox protein, is reported to be upregulated in LUAD. However, its regulatory role in LUAD progression warrants in-depth investigation. This study highlights the dual impact of CBX4 on LUAD proliferation and metastasis. Through a series of rigorous in vitro and in vivo experiments, we elucidate that CBX4 functions in promoting LUAD proliferation via upregulating PHGDH expression while concurrently suppressing LUAD metastasis by inhibiting ZEB2 transcription. Further investigation into the underlying mechanism reveals CBX4’s intricate interactions with distinct epigenetic factors. The inhibition of ZEB2 transcription involves CBX4-mediated recruitment of canonical PRC1 (cPRC1), establishing H2K119ub on the ZEB2 promoter. Simultaneously, CBX4 facilitates PHGDH transcription through interaction with GCN5, inducing heightened histone acetylation on the PHGDH promoter. These findings underscore CBX4's pivotal role as a regulator of LUAD progression, emphasizing its diverse transcriptional regulatory functions contingent upon interactions with specific epigenetic partners. Understanding the nuanced interplay between CBX4 and epigenetic factors sheds light on potential therapeutic avenues in LUAD.
2024-01-05 | GSE252230 | GEO