Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA384842 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Next-generation Sequencing of Small Cell Lung Cancer to Identify Actionable Targets for Treatment
| PRJNA384841 | ENA
Project description:We obtained small cell lung cancer specimens and normal lung specimens from patients who died of drug-resistant SCLC. The small lung cancer specimens include primary lesions and metastatic lesions. Next generation sequencing was performed to assess the expression of miRNA in drug-resistant small cell lung cancer.
2021-06-05 | GSE176198 | GEO
Project description:Next Generation Sequencing (RNAseq) of non-small cell lung cancer
| PRJNA320473 | ENA
Project description:In the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the emergence of acquired resistance remains a significant challenge. Elucidating the underlying mechanisms of resistance is crucial for developing novel strategies to overcome or delay therapeutic escape. To this end, this study aimed to identify key drivers of EGFR-TKIs resistance and explore actionable targets for intervention. We investigated resistance mechanisms by integrating CRISPR/Cas9-based genome-wide screening with tandem mass tag (TMT) proteomic analysis, and virtually screened bioactive small molecule libraries to identify compounds capable of restoring EGFR-TKIs sensitivity. The multi-omics approach revealed that CCT2 is a critical mediator of resistance to third-generation EGFR-TKIs in lung cancer, with higher expression of CCT2 observed in resistant cells compared to sensitive cells. Mechanistically, CCT2 recruits tripartite motif-containing protein 28 (TRIM28) to catalyze SUMO2 modification of thioredoxin-related transmembrane protein 1 (TMX1), inhibiting its ubiquitination and enhancing protein stability. This post-translational modification (PTM) promotes TMX1-dependent reactive oxygen species (ROS) clearance, thereby conferring resistance. Importantly, pharmacological inhibition with the compound HY-10127, identified through virtual screening, effectively restored EGFR-TKIs sensitivity in resistant cell lines and delayed the development of resistance in xenograft models. The findings establish the CCT2/TRIM28/TMX1/ROS axis as a novel resistance mechanism in EGFR-mutated lung cancer, and targeting this pathway with HY-10127 represents a promising strategy to overcome resistance to third-generation EGFR-TKIs, providing preclinical rationale for clinical translation. These discoveries advance our understanding of molecular resistance mechanisms and offer potential therapeutic targets for improving lung cancer prognosis.
2025-07-26 | PXD066633 |
Project description:Non-small cell lung cancer (NSCLC) death rates exceed the next 3 prevalent cancers combined; however, most NSCLC tumors lack actionable mutations. Recent studies of NSCLC and other cancers revealed profound proteome remodelling with prognostic impact that is not fully predicted by DNA or RNA analyses. These revelations portend proteome-based cancer classification and treatment. This will require model systems that recapitulate tumor proteomes and phenotypes. A subset (~35%) of the most aggressive NSCLC can form a patient-derived xenograft (PDX). We generated 137 PDX models of aggressive NSCLC, which represent the histological, genome, transcriptome, and DNA methylation features and proteome remodelling of primary NSCLC. The models indicate 3 lung adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, candidate targets, and in adenocarcinoma, distinct stromal immune features. The PDX resource will foster proteome-directed stratification and development of new treatments for aggressive NSCLC.
2021-11-23 | GSE166997 | GEO
Project description:Non-small cell lung cancer (NSCLC) death rates exceed the next 3 prevalent cancers combined; however, most NSCLC tumors lack actionable mutations. Recent studies of NSCLC and other cancers revealed profound proteome remodelling with prognostic impact that is not fully predicted by DNA or RNA analyses. These revelations portend proteome-based cancer classification and treatment. This will require model systems that recapitulate tumor proteomes and phenotypes. A subset (~35%) of the most aggressive NSCLC can form a patient-derived xenograft (PDX). We generated 137 PDX models of aggressive NSCLC, which represent the histological, genome, transcriptome, and DNA methylation features and proteome remodelling of primary NSCLC. The models indicate 3 lung adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, candidate targets, and in adenocarcinoma, distinct stromal immune features. The PDX resource will foster proteome-directed stratification and development of new treatments for aggressive NSCLC.
2021-11-23 | GSE166998 | GEO
Project description:Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers. Lymphatic metastasis serves as a predominant NSCLC metastatic route and an essential predictor of patient prognosis. Recently, circular RNA (circRNA) has emerged as critical mediator in various tumor initiation and progression. To identify essential circRNA that involves in the lymphatic metastasis of NSCLC, Next generation sequencing (NSG) was performed in 6 paired NSCLC tissues and normal adjacent tissues (NAT).
2023-12-01 | GSE235634 | GEO
Project description:The expression profiles of miRNAs in drug-resistant non-small cell lung cancer (NSCLC) cell lines were identified via next generation sequencing and the common dysregulated miRNAs in drug-resistant NSCLC cell lines were picked up for further analysis.
2020-11-01 | GSE122452 | GEO
Project description:Immunotherapy has shown great therapeutic potential for cancers with high tumor mutational burden (TMB), but much less promise for cancers with low TMB. One primary approach for adoptive lymphocyte transfer-based immunotherapy is to target the somatic mutated peptide neoantigens and cancer testis (CT) antigens recognized by cytotoxic T cells. Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ- associated peptides in both melanoma, a “hot tumor”, and EGFR mutant lung adenocarcinoma, a “cold tumor”. We uncovered 19 common driver oncogene-derived peptides and more than 1000 post-translationally modified peptides (PTM) representing 58 different PTMs. We constructed a CT antigen database with 286 antigens by compiling reputed CT antigen resources and “in-house” genomic data and used this to identify 45 CT antigen-derived peptides from the identified HLA peptidome. Using integrated next generation sequencing data, we discovered 12 neopeptides in EGFR mutant lung cancer cell lines. Finally, we report a novel approach for non-canonical peptide discovery, whereby we leveraged a deep learning-based de novo search and a high confidence annotated long noncoding RNA (LncRNA) database to identify 44 lncRNA-derived peptides. Findings of this study, for the first time, provide evidence for a large pool of actionable cancer antigen-derived peptides for use in mutant EGFR lung cancer immunotherapy.
2021-12-07 | PXD019774 | Pride