CTPS1-Mediated Malignant Phenotypes and Targeted Intervention in Lung Adenocarcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Guangshun Wang
PROVIDER: PXD076132 | iProX | Tue Mar 24 00:00:00 GMT 2026
REPOSITORIES: iProX
Similar Datasets
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers Array comparitive genomic hybridization analysis of 29 Lung Adenocarcinomas with Bronchioalveolar Features.
2008-07-01 | E-GEOD-11945 | biostudies-arrayexpress
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers
2008-07-01 | GSE11945 | GEO
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
2024-09-02 | BIOMD0000000827 | BioModels
Project description:Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remains unclear. This study aimed to establish the circular RNA expression profile of lung adenocarcinoma tissue and determine its potential diagnostic and prognostic value.
2023-03-09 | GSE146689 | GEO
Project description:Purpose: Serum markers that enable diagnosis in the early stage of lung cancer have not been discovered. We have developed a LC-MRM-MS assay for the identification of potential early marker proteins for lung adenocarcinoma.
Experimental design: LC-MRM-MS assay was used for measuring the level of 35 candidate peptides in plasma from 102 lung adenocarcinoma patients (including n=50, 16, 24, and 12 in stage I, II, III, and IV, respectively.) and 84 healthy controls. Stable isotope labeled standard peptides were synthesized to accurately measure the amount of these proteins.
Results: Seven proteins were found to be able to distinguish stage I patients from controls. These proteins were combined in to a protein marker panel which improved the sensitivity to discriminate stage I patients from controls and resulted in a high classification performance with cross-validated area under the curve=0.76. Besides, we found that low expression of eukaryotic initiation factor 4A-I and high expression of lumican showed significantly poor prognosis in overall survival (p=0.012 and 0.0074, respectively), which may be used as prognostic biomarkers for lung cancer.
Conclusion and clinical relevance: Proteins highlighted here may be used for early detection of lung adenocarcinoma or therapeutics development after validation in a larger cohort.
2021-01-24 | PXD014683 | panorama
Project description:This study characterizes transcriptional changes associated with osteogenic induction in pancreatic ductal adenocarcinoma (PDAC) cell lines. Capan-2 and PANC-1 cells were cultured under control conditions or osteogenic induction and collected at day 0, day 7, and day 14. Bulk RNA sequencing was performed to identify gene expression dynamics during osteogenic reprogramming. Analyses revealed activation of osteogenic markers and related pathways, along with suppression of cell-cycle programs. These datasets provide a transcriptomic framework for understanding osteogenic plasticity in PDAC cells.
2026-06-18 | GSE314240 | GEO
Project description:The tumor microenvironment (TME) not only influences cancer progression but has also been shown to have a significant impact on patient prognosis. One of the major TME components is cancer-associated fibroblasts (CAFs), of which several subtypes are identified in tumor tissues. Although scRNA-seq technology is a powerful tool to investigate the cellular proportion and composition in tissues, large-scale datasets are required to analyze a small number of cell populations. Here, we constructed an integrated single-cell RNA-seq dataset for non-small cell lung cancer (NSCLC) by compiling publicly-available data and demonstrated differences in TME heterogeneity and cellular composition between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Particularly, we identified significant differences in CAF subtypes between LUAD and LUSC. Inflammatory CAFs (iCAFs) were dominantly found in LUAD, while myofibroblastic CAFs (mCAFs) were more common in LUSC. Co-culture analysis with lung fibroblasts confirmed that LUAD cells induced iCAF phenotype and, in contrast, LUSC promoted myofibroblastic differentiation. Correlation analysis with patient prognosis identified mCAF as a poor prognostic factor in both LUAD and LUSC, but iCAF was found to be a poor prognostic factor only in LUSC, and vice versa in LUAD. This work highlights important considerations on CAF subtype dominance in LUAD and LUSC, which may relate to patient prognosis.
2025-08-29 | GSE298868 | GEO
Project description:Genome wide DNA methylation profiling of Stage I Lung Adenocarcinoma and non-tumor adjacent tissues. The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included tumor and adjacent non-tumor tissues excised from a cohort of 35 patients with Stage I Lung Adenocarcinoma. Candidate prognostic biomarkers were validated by pyrosequencing in independent cohorts.
2015-04-30 | GSE63384 | GEO
Project description:Through a metabolic RNAi-based screen for cell invasion, potential metastatic functions of AASS were identified. This study was to investigate the role of AASS and its metabolic product, α-aminoadipate (2-AAA), in the metastatic potential of lung adenocarcinoma. H1299 lung adenocarcinoma cells were infected with a pLKO.1-based lentiviral vector carrying shRNA targeting AASS. Poly-A RNA sequencing was then performed on control and AASS-knockdown H1299 cells to assess differentially expressed genes modulated by AASS depletion.
2026-02-28 | E-MTAB-16032 | biostudies-arrayexpress
Project description:Proteomic analyses identify dysregulated proteins and pathways between low-risk and high-risk subtype of early-stage lung adenocarcinoma and their prognostic impacts.Sample labels: A,low-risk tumor;B,low-risk normal;C,high-risk tumor;D,high-risk normal.
2020-07-18 | MSV000085775 | MassIVE