ArticleCancer research2022
High-Resolution Profiling of Lung Adenocarcinoma Identifies Expression Subtypes with Specific Biomarkers and Clinically Relevant Vulnerabilities.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations.Nature communications · 2025Trial
- Artificial Intelligence-Powered Human Epidermal Growth Factor Receptor 2 Quantification and Clinical Outcomes in Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Cancer Treated With Trastuzumab Plus Folinic Acid, Fluorouracil, and Oxaliplatin.JCO precision oncology · 2025Trial
- Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.iScience · 2026Article
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- SMARCA4 activation engages FOSL1 to drive enhancer reprogramming and tumorigenic phenotypes in SMARCA4-deficient LUAD cells.Cell death discovery · 2026Article
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- B cell-reactive neoantigens boost antitumor immunity.Science advances · 2025Article
- LOSTdb: a manually curated multi-omics database for lung cancer research.BMC bioinformatics · 2025Article
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures.Cancer cell · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Spatial transcriptomic analysis across histological subtypes reveals molecular heterogeneity and prognostic markers in early-stage lung adenocarcinoma.Clinical and translational medicine · 2025Article
- Identification of breast cancer subtypes and drug response prediction through forward and reverse translation.NPJ precision oncology · 2025Article
- Novel TEAD1 Inhibitor VT103 Enhances Dabrafenib Efficacy in BRAF V600E Mutated Lung Adenocarcinoma via Survivin Downregulation.Cancer science · 2025Article
- FAM207A acts as a novel and potential biomarker in lung adenocarcinoma and shapes the immunesuppressive tumor microenvironment.Clinical and experimental medicine · 2025Article
- Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.Cancer cell · 2025Article
- Article
- Integration of multi-omics and single-cell transcriptome reveals mitochondrial outer membrane protein-2 (MTX-2) as a prognostic biomarker and characterizes ubiquinone metabolism in lung adenocarcinoma.Journal of Cancer · 2025Article
- SyntheVAEiser: augmenting traditional machine learning methods with VAE-based gene expression sample generation for improved cancer subtype predictions.Genome biology · 2024Article
- Dissecting transcriptome signals of anti-PD-1 response in lung adenocarcinoma.Scientific reports · 2024Article
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14 authors.
Funding
Abstract
Lung adenocarcinoma (LUAD) is one of the most common cancer types and has various treatment options. Better biomarkers to predict therapeutic response are needed to guide choice of treatment modality and to improve precision medicine. Here, we used a consensus hierarchical clustering approach on 509 LUAD cases from The Cancer Genome Atlas to identify five robust LUAD expression subtypes. Genomic and proteomic data from patient samples and cell lines was then integrated to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency profiles. Subtype 4 (S4)-associated cell lines exhibited specific vulnerability to loss of CDK6 and CDK6-cyclin D3 complex gene (CCND3). Subtype 3 (S3) was characterized by dependency on CDK4, immune-related expression patterns, and altered MET signaling. Experimental validation showed that S3-associated cell lines responded to MET inhibitors, leading to increased expression of programmed death-ligand 1 (PD-L1). In an independent real-world patient dataset, patients with S3 tumors were enriched with responders to immune checkpoint blockade. Genomic features in S3 and S4 were further identified as biomarkers for enabling clinical diagnosis of these subtypes. Overall, our consensus hierarchical clustering approach identified robust tumor expression subtypes, and our subsequent integrative analysis of genomics, proteomics, and CRISPR screening data revealed subtype-specific biology and vulnerabilities. These LUAD expression subtypes and their biomarkers could help identify patients likely to respond to CDK4/6, MET, or PD-L1 inhibitors, potentially improving patient outcome. SIGNIFICANCE: Integrative analysis of multiomic and drug dependency data uncovers robust lung adenocarcinoma expression subtypes with unique therapeutic vulnerabilities and subtype-specific biomarkers of response.
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