A5087338217- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Gastrointestinal Tumor Research and Treatment
- Chromatin Remodeling and Cancer
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Radiomics and Machine Learning in Medical Imaging
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- Gastric Cancer Management and Outcomes
- HER2/EGFR in Cancer Research
- Cancer, Stress, Anesthesia, and Immune Response
- Ferroptosis and cancer prognosis
- Immunotherapy and Immune Responses
- Cancer-related gene regulation
Duke-NUS Medical School
2022-2025
Abstract Gastric cancer (GC) is a major cause of global mortality with high levels heterogeneity. To explore geospatial interactions in tumor ecosystems, we integrated 2,138 spatial transcriptomic regions-of-interest (ROIs) 152,423 single-cell expression profiles across 226 GC samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating progression through spatially localized and functionally ordered subgroups associated specific immune...
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased cancer (GC) risk. Analyzing 1,256 samples (1,152 IMs) across 692 subjects from prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell spatial profiles highlight changes tissue ecology lineage heterogeneity, an stem-cell dominant cellular compartment linked to early malignancy....
Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, tumor microenvironment (TME) features that contribute peritoneal organotropism GC.
Objective Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining studies, we derived and applied consensus Mes-GC classifier to define the enhancer landscape revealing disease vulnerabilities. Design Transcriptomic profiles of ~1000 primary GCs cell lines were analysed derive classifier. Clinical genomic associations performed across >1200 patients...
Objective Gastric cancer (GC) is a leading cause of mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher -specific GC regulatory networks and examine therapeutic vulnerabilities arising from loss. Design Genomic profiling patients including Singapore cohort (>200 patients) was performed derive mutational signatures inactivation across molecular subtypes. Single-cell transcriptomic profiles -mutated GCs were analysed tumour...
218 Background: Peritoneal metastases (PM) in colorectal cancer (CRC) portend a poor prognosis. We sought to elucidate spatially resolved molecular features facilitating transcoelomic dissemination and progression. Methods: 50 PT, 116 PM 37 primary normal samples from 96 patients were retrieved profiled with digital spatial profiling (GeoMx DSP, Nanostring Technologies). Through unsupervised clustering, we characterized the microenvironment of tumor-stroma compartments studied roles stromal...
Abstract Background Within the tumor microenvironment (TME), association of B lymphocytes (B cells) with prognosis and therapy response in gastric cancer (GC) remains poorly characterized. We investigated predictive prognostic value cells, including their spatial organization within TME, one largest multi-cohort studies to date. Methods Using CD20 immunohistochemistry, we evaluated cell density resection specimens from 977 patients resectable GC across three cohorts, randomized phase III...
<div>Abstract<p>Gastric cancer is a major cause of global mortality. To explore geospatial interactions in gastric tumors, we integrated 2,138 spatial transcriptomic regions interest with 152,423 single-cell expression profiles across 226 samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating tumor progression through spatially localized and functionally ordered subgroups associated specific immune microenvironments, checkpoint...
<p>(1) Supplementary Figure 1 shows morphologies of different ROI categories and their representative genes, pathways similarities with paired scRNA-seq data. (2) 2 validation findings from the discovery GeoMx DSP cohort in whole-section also TMA cohort. (3) 3 experiments validating that intratumor G1/G2 subregion expression is tumor-intrinsic using multiplexed IHC, Stereoseq spatial transcriptomics, vitro drug treatment profiling. (4) 4 individual immune checkpoints, chemokines,...
We evaluated the relevance of PD-1+CD8+ T-cells in gastric cancer (GC) including prognostic significance, association with chemotherapy and immunotherapy sensitivity correlations tumor microenvironment (TME).Discovery cohort: GC samples were for AE1/3, CD8, PD-1, Ki-67 Granzyme-B expression fluorescence-based multiplex immunohistochemistry (mIHC). Validation cohorts: we analyzed bulk RNAseq datasets from TCGA, "3G" trial an phase 2 trial. The cox proportional hazards model was used to...
Abstract Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased cancer (GC) risk. We analyzed 1256 samples (1152 IMs) from 692 subjects through prospective 10-year study. identified 26 IM driver genes in diverse pathways including chromatin regulation ( ARID1A ) and intestinal homeostasis SOX9 ), largely occurring as small clonal events. Analysis dynamics between within subjects, also longitudinally across time, revealed that clones are likely...
Abstract Background: The poor prognosis of peritoneal metastasis (PM) in colorectal cancer (CRC) is typically attributed to, and characterized by, resistance to systemic chemotherapy immunotherapy. evolutionarily conserved plasma-peritoneal barrier as well reduced tumor tissue vascularity contributes poorer responses systemically administered antineoplastic therapy. Beyond these, we sought understand transcriptomic variations important therapeutic targets implicated organotropism by...
Abstract Background: Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis. Yet, biological mechanisms underpinning peritoneal colonization and transcoelomic remain unclear. Utilizing novel humanized mouse model of GCPM, we seek to understand the evolution peritoneum allow for dissemination. The model, defined as mice engrafted with functional human cells or tissues, was selected host immune system appears play significant role metastases. Methodology: Humanized (humice)...
Abstract Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis, yet our understanding of tumor microenvironmental (TME) characteristics associated with GCPM remain limited. Here, we analyzed intrinsic genomic alterations and transcriptomic programs predictive prospective cohort 248 patients, identifying CDH1 , PIGR ELF3 mutations as predictors. By inspecting the spatial dynamics TME, find that compartment infiltration pro-tumorigenic cell types such inflammatory...
Abstract Objective Gastric cancer (GC) is a leading cause of mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher ARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising from loss. Design Genomic profiling patients including Singapore cohort (&gt;200 patients) was performed derive mutational signatures inactivation across molecular subtypes. Single-cell transcriptomic profiles ARID1A-mutated GCs were...
Abstract Gastric cancer (GC) is a major cause of global mortality with high heterogeneity levels. To explore geospatial interactions in tumor ecosystems, we integrated 1,563 spatial transcriptomic regions-of-interest (ROIs) 152,423 single-cell expression profiles across 130 GC samples from 70 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating progression through spatially localized and functionally ordered subgroups specific immune microenvironments...
Abstract PURPOSE HER2-positive gastric cancer (HER2+ GC) exhibits significant intra-tumoral heterogeneity and frequent development of resistance to HER2-targeted therapies. This study aimed characterize the spatial tumor microenvironment (TME) in HER2+ GC identify mechanisms HER2 blockade including trastuzumab deruxtecan (T-DXd), with goal informing novel therapeutic strategies. PATIENTS AND METHODS We performed transcriptomics on pre-and post-treatment samples from patients metastatic who...