Angie Lay Keng Tan
A5109503508- RNA modifications and cancer
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Gastric Cancer Management and Outcomes
- Pancreatic and Hepatic Oncology Research
- Gastrointestinal Tumor Research and Treatment
- Bladder and Urothelial Cancer Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Viral-associated cancers and disorders
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
Duke-NUS Medical School
2014-2025
Weatherford College
2023
Gastric cancer heterogeneity represents a barrier to disease management. We generated comprehensive single-cell atlas of gastric (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage exhibited cancer-associated expression profiles, individually contributing combined tumor-wide molecular collage. observed increased plasma proportions in diffuse-type...
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...
<h3>Objective</h3> Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought validate these findings, investigate how factors function promote GC, identify potential treatment GCs harbouring amplifications. <h3>Design</h3> <i>KLF5</i>, <i>GATA4</i> <i>GATA6</i> copy number gene expression was examined multiple GC cohorts....
Abstract Background Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform (Iso-Seq) and Illumina paired-end comprehensively survey the transcriptome gastric cancer (GC), leading cause global mortality. Results We performed full-length analysis across 10 GC cell lines covering four major molecular subtypes (chromosomal unstable, Epstein-Barr positive,...
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...
<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,...
Objective Gastric cancer (GC) is a leading cause of mortality. Previous studies have shown that hepatocyte nuclear factor-4α (HNF4α) specifically overexpressed in GC and functionally required for development. In this study, we investigated, on genome-wide scale, target genes HNF4α oncogenic pathways driven by genes. Design We performed chromatin immunoprecipitation followed sequencing across multiple cell lines, integrating occupancy data with (epi)genomic transcriptome primary GCs to define...
MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or targets. Currently, only a limited number miRNAs have been functionally linked to specific pathways. Here, we explored if gene expression signatures could be used represent miRNA activities and integrated with genomic oncogenic activity identify connections between pathways on high-throughput, genome-wide scale. Mapping >300 >700 primary tumor profiles, constructed miRNA–pathway...
Abstract The switch between quiescence and proliferation is central for neurogenesis its alteration linked to neurodevelopmental disorders such as microcephaly. However, intrinsic mechanisms that reactivate Drosophila larval neural stem cells (NSCs) exit from are not well established. Here we show the spindle matrix complex containing Chromator (Chro) functions a key regulator of NSC reactivation downstream extrinsic insulin/insulin-like growth factor signalling. Chro also prevents NSCs...
Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark cancer, occurring in 90% human malignancies. However, specific mechanisms driving TERT remain obscure for many tumor types and particular gastric cancer (GC), leading cause global mortality. Here, through comprehensive genomic epigenomic analysis primary GCs GC cell lines, we identified the transcription factor early B 1 (EBF1) as transcriptional repressor inactivation EBF1 function major upregulation....
Abstract Background Enhancers are distal cis -regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted regions remain to be functionally tested. Methods We analyzed 132 epigenomic histone modification profiles 18 primary gastric cancer (GC) samples, normal tissues, 28 GC lines using Nano-ChIP-seq technology. applied Capture-based...
Abstract Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) multiple cancers. Here, we discovered that besides its well-established role repair, exerts a novel epigenomic function gastric cancer. Unbiased CRISPR-based mass spectrometry combined with genome-wide CRISPR functional screening revealed early-stage cancer genomic binding is not randomly distributed but rather associated specifically tumor-associated super-enhancers controlling...
Abstract Gastric cancer cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic gastric cancer. To achieve greater benefits, selection of patients eligible this treatment is critical. Although gene expression profiling widely used a genomic classifier to identify molecular subtypes and stratify different regimens, its prediction accuracy can be improved....
Abstract Background CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying remain poorly understood. We sought to discover contributors GC, by performing global DNA methylation, gene expression, proteomics profiling across 14 cell lines, followed similar integrative analysis 50 GC lines 467 primary GCs....
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...
392 Background: Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis. Yet, there are paucity of data on underlying genomic alterations predictive GCPM. Methods: Two-hundred and nine patients who underwent primary tumor (PT) surgical resection were included the prospective cohort. Whole exome sequencing (WES) these resected PT GC specimens (average coverage 129X for samples, 70X matched normal/blood controls) undertaken. Participants followed-up longitudinally peritoneal...
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 Gastric cancer is highly heterogeneous. To analyze their biology, patient-derived organoids (PDOs) are useful because they maintain intra-tumor heterogeneity (ITH) as well inter-patient heterogeneity. Recently, four groups reported the establishment of gastric PDOs. However, it still not easy need to overcome a common problem: “contamination” culture with “non-cancer cell”-derived from specimen. These non-cancer often overgrow and became dominant. Furthermore, PDOs have another...