Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/226216
Title: DISSECTING THE HETEROGENEITY OF GASTRIC CANCER AT THE SINGLE CELL LEVEL
Authors: RAMNARAYANAN KALPANA
Keywords: Single-cell sequencing, Gatric cancer, atlas, tumor microenvironment
Issue Date: 17-Nov-2021
Citation: RAMNARAYANAN KALPANA (2021-11-17). DISSECTING THE HETEROGENEITY OF GASTRIC CANCER AT THE SINGLE CELL LEVEL. ScholarBank@NUS Repository.
Abstract: Heterogeneity between and within gastric cancers (GCs) represents a significant impediment in disease management, underpinned by a poor understanding of lineage-states resident across distinct GC subtypes. We generated a large single-cell atlas of GC (>200,000 cells) from primary gastric tumor samples representing clinical stages and Lauren's histological subtypes. We identified 34 distinct cell-lineage states, connected via developmental trajectories and previously unreported rare cell populations. We observed increased plasma cell proportions as a feature of diffuse-type tumors associated with epithelial KLF2, and a stage-wise accrual of novel cancer-associated fibroblast sub-populations marked concurrently by high FAP and INHBA co-expression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences. We complement these findings using spatial transcriptomics, orthogonal validation in independent bulk RNA-seq cohorts, and functional demonstration in in vitro and in vivo models. Our results identify unique cancer-lineage programs delineating both intra- and inter-patient differences in the tumor milieu, providing a high-resolution molecular resource for GC translational studies.
URI: https://scholarbank.nus.edu.sg/handle/10635/226216
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