Brain metastasis from lung adenocarcinoma patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Don Nguyen
PROVIDER: E-GEOD-14108 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.
2010-06-17 | GSE14108 | GEO
Project description:Transcriptomic profiling of Lung adenocarcinoma brain metastasis
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Project description:Brain metastasis developed in nearly 40% of lung adenocarcinoma (LUAD) patients diagnosed with distant metastasis. There is lack of transcriptomic data of brain lesions from human lung adenocarcinoma patients. As part of the project to understanding the tumor microenvironment in brain metastasis of LUAD patients, we performed bulk RNA analysis on brain metastases from 6 LUAD patients. In order to understand the tumor intrinsic factors that potential shape the tumor microenvironment, we compared these data with bulk RNA sequencing data from 14 early stage and 11 late stage primary LUAD tumor from TCGA database. Pathway expression analysis showed a downregulation of pro-inflammatory signals in brain metastasis and upregulation of DNA synthesis and oxidative phosphorylation pathways related to rapid proliferation in brain lesions.
2019-12-10 | GSE141685 | GEO
Project description:Brain metastasis significantly contributes to the failure of targeted therapy in patients with EGFR-mutated lung adenocarcinoma (LUAD). Reduced expression of RBM10 is associated with brain metastasis in these patients. However, the mechanism by which RBM10 affects brain metastasis in EGFR-mutated LUAD remains unclear. Previous studies reveal that RBM10 mutations lead to decreased expression and deregulated splicing at a subset of junctions, primarily through exon skipping.
2025-03-19 | GSE280915 | GEO
Project description:Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30-55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to establish brain metastasis cell lines, though traditional methods have limitations such as high costs, lengthy timeframes, and the need for specialized imaging equipment. To address these issues, we developed an improved approach by performing low cell number circulating intracranial injections (500-4000 cells) in nude mice, successfully establishing the H1975-BM1, BM2, and BM3 cell lines. Through RNA sequencing and bioinformatics analyses, we identified transcriptomic differences among these cell lines, revealing that H1975-BM1 cells primarily exhibit stem cell function and migration characteristics, while H1975-BM3 cells display enhanced chemotaxis, cell adhesion, and cytokine secretion associated with interactions. Experimental validation, including Transwell assays, CCK8, cell adhesion assays, and subcutaneous tumor implantation in nude mice, further confirmed these findings, with H1975-BM3 forming larger tumors and a more pronounced secretion cystic cavity. In conclusion, our improved methodology successfully established high-confidence brain metastasis lung adenocarcinoma cell lines, elucidating distinct transcriptomic and functional characteristics at different stages of brain metastasis progression.
2025-05-30 | GSE297016 | GEO
Project description:Brain metastases are common in lung adenocarcinoma (LUAD) patients, and by far, the metastasis mechanisms are not fully understood. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with CTC, primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. we obtained a more comprehensive picture over lung cancer metastasis in the single-cell level, giving a new perspective to the role of RAC1 in the LUAD brain metastasis, and related pathways to participate in the metastasis process.
2022-03-13 | GSE198291 | GEO
Project description:Background: Claudin-1(CLDN1), one of the key components of tight junction proteins, was found to be down-regulated in human lung adenocarcinomas. This study we investigated the clinical significance of CLDN1 expression in lung adenocarcinoma patients and its role in cancer progression. Method: CLDN1 mRNA expression was measured in tumor specimens from 51 patients with lung adenocarcinoma. CLDN1 protein expression was also examined by immunohistochemistry on specimens from an independent cohort of 67 lung adenocarcinoma patients. CLDN1 and cancer cell migration, invasion, and in vivo metastasis were studied by compared CLDN1 overexpressed, specific shRNA knockdown cells and controls. The Affymetrix oligonucleotide microarray analysis was performed to identify CLDN1 downstream genes. Results: Lung adenocarcinoma patients with low expression of CLDN1 mRNA had shorter overall survival (p = 0.032, log-rank test). This result was further confirmed by immunohistochemistry of CLDN1 protein expression in an independent cohort of lung adenocarcinoma patients (p=0.024). Over-expression of CLDN1 inhibited lung adenocarcinoma cell migration, invasion, and in vivo metastasis. Knockdown of the exogenous CLDN1 expression in CLDN1 transfectants can restore the cancer cell invasive and metastatic ability. By using Affymetrix microarray we have identified panel of genes altered by CLDN1 over-expression. CLDN1 can up-regulate several cancer invasion/metastasis suppressors such as CTGF, THBS1, DLC1, OCLN, ZO-1, and also down-regulate invasion/metastasis enhancers such as SPP1, CUTL1, TGF-α, SLC2A3, PGF, which support that CLDN1 may behave as an invasion and metastasis suppressor. Conclusions: CLDN is a cancer invasion and metastasis suppressor. CLDN1 expression is a useful prognostic predictor and a potential drug treatment target for lung adenocarcinoma patients. Keywords: genetic modification
2008-12-23 | GSE10309 | GEO
Project description:Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain types of cancers. How cell lineage restricted genes specifically influence metastatic progression is poorly defined. In lung cancers, we uncovered an alveolar cell-selective transcriptional program that preferentially correlates with lung adenocarcinoma metastasis. This program is required for epithelial specification in the distal airways and is partially regulated by the lineage transcription factors GATA6 and HOPX. These factors cooperatively restrain the metastatic competence of adenocarcinoma cells, without affecting their survival, through the modulation of alveologenic and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links alveolar cell fate with metastasis suppresion in the lung adenocarcinoma subtype. mRNA profiles of human lung Adenocarcinoma PC9 cell lines infected with lentivirus harboring shRNA of control (Arab1) and shRNA of both GATA6 and HOPX were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
2013-06-10 | E-GEOD-39121 | biostudies-arrayexpress
Project description:Background: Brain metastasis, a leading cause of death in patients with lung adenocarcinoma (LUAD), arises from tumor cells adapting to the brain’s unique microenvironment of the brain through metabolic remodeling regulated by key oncogenes. Here, we aimed to determine the role of high mobility group protein B3 (HMGB3) in regulating tumor cell metabolism to promote the progression and brain metastasis in LUAD. Methods: In this study, a LUAD cell model predisposed to brain metastasis was developed in this study, and differentially expressed genes HMGB3 was identified. HMGB3 expression in LUAD was then validated through a series of in vitro and in vivo experiments, including western blotting, single-cell RNA sequencing (scRNA-seq), and immunohistochemistry (IHC). Tissue microarray (TMA) and LUAD brain metastasis clinical samples were used to explore the expression of HMGB3 and its clinical significance in LUAD. Additionally, we performed gene enrichment analysis on scRNA-seq and bulk RNA-seq, along with western blotting, to identify the pathways through which HMGB3 may cause brain metastasis. We then used coimmunoprecipitation and mass spectrometry to identify protein single-stranded DNA binding protein 1 (SSBP1), which interacts with HMGB3. Finally, gain and loss-of-function and rescue experiments were conducted to study SSBP1’s roles in LUAD cells. Results: HMGB3 upregulation in LUAD primary tumors and brain metastases associated with poor prognosis independent of metastasis. HMGB3 enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) capabilities of LUAD cells in vitro and promotes the occurrence and development of brain metastasis in vivo. Mechanistically, HMGB3 recruited SSBP1, inducing its nuclear translocation and reprogramming mitochondrial metabolism, thereby increasing cytoplasmic reactive oxygen species (ROS) levels, which activated the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) pathway by downregulating phosphatase and tensin homolog (PTEN), enhancing tumor cell proliferation, migration, invasion, and EMT. Conclusions: This study demonstrated that HMGB3 functions as a driver gene in the brain metastasis of LUAD, promoting metabolic adaptation of tumor cells to the brain microenvironment through the regulation of mitochondrial metabolism, thereby offering potential therapeutic targets for LUAD brain metastases.
2025-12-31 | GSE293936 | GEO
Project description:Patients undergoing pancreatic resection at William Beaumont Hospital (Royal Oak, MI) were consented prior to surgery with local IRB oversight. Samples were collected at time of surgery and stored at -80°C according to CAP (College of American Pathologist)-accredited standard operating procedures. Disease pathology of frozen samples was validated with hematoxylin and eosin stained tissue sections from adjacently collected formalin fixed paraffin embedded tissue. The objective of this study was to examine the gene expression patterns of pancreatic adenocarcinoma treated with neoadjuvant chemoradiotherapy compared to pancreatic adenocarcinoma that had not under gone neoadjuvant treatment. The results of this study demonstrate that neoadjuvant therapy alters the gene expression of pancreatic adenocarcinoma
2015-10-01 | GSE60646 | GEO