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Single-cell atlas of lineage states, tumor microenvironment and subtype specific expression programs in gastric cancer

ABSTRACT: Gastric cancer (GC) heterogeneity between and within tumors represents a barrier to disease management. We generated a comprehensive single-cell atlas of GC comprising 31 primary gastric tumor samples representing clinical stages I-IV and histological subtypes. We identified 34 distinct cell-lineage states, related by developmental trajectories and previously unreported rare cell populations. Many lineage states exhibited a distinctive tumor-associated expression profile, each contributing individually to a combined tumor-wide molecular collage. We observed increased plasma cell proportions as a feature of diffuse-type tumors associated with epithelial-resident KLF2, and a stagewise accrual of novel cancer-associated fibroblast sub-populations marked by high INHBA and FAP co-expression. Our results provide a high-resolution molecular resource for GC translational studies, identifying intra- and inter-patient lineage-states across distinct GC subtypes. #### GEO title mapping with the ID in PMID:34642171 #### Manuscript_ID Primary_Tumor Primary_Normal Peritoneal_Tumor Peritoneal_Normal NGCII521 sample7.csv sample6.csv - - NGCII513 sample22.csv sample21.csv - - NGCII512 sample26.csv sample25.csv - - NGCII520 sample5.csv sample4.csv - - NGCII514 sample24.csv sample23.csv - - NGCII518 sample2.csv sample1.csv - - NGCII525 sample10.csv sample9.csv - - NGCII527 sample12.csv sample11.csv - - NGCII538 sample36.csv sample35.csv sample38.csv sample37.csv NGCII539 sample32.csv - - - NGCII529 sample13.csv - - - NGCII511 sample15.csv - - - NGCII498 sample18.csv - - - NGCII522 sample29.csv - - - NGCII499 sample16.csv - - - NGCII502 sample14.csv - - - NGCII509 sample17.csv - - - NGCII540 sample33.csv - - - NGCII541 sample34.csv - - - NGCII543 sample39.csv - - - NGCII510 sample27.csv - - - NGCII519 sample3.csv - - - NGCII531 sample28.csv - - - NGCII545 sample40.csv - - - NGCII533 sample30.csv - - - NGCII524 sample8.csv - - - NGCII536 - sample31.csv - - NGCII011 - - sample19.csv - NGCII015 - - sample20.csv -

ORGANISM(S): Homo sapiens

PROVIDER: GSE183904 | GEO | 2021/10/05

REPOSITORIES: GEO

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Project description:Background: Intestinal metaplasia (IM) is a gastric precancerous lesion that precedes the development of gastric cancer in up to 3.77 cases/1000 person-years. It consists in a trans-differentiation process of gastric to intestinal tissue. Two histological subtypes exist, complete (CIM) and incomplete (IIM), the latter having higher progression rates to gastric cancer . Our objective was to identify molecular processes responsible for the tumoral transition from intestinal metaplasia to GC and the initial steps of this lesion Methods: We used expression microarray to compare the transcriptome of intestinal metaplasia subtypes that progress to gastric cancer (IIM-GC and CIM-GC) after a follow-up period with respect to those that do not progress (IIM control and CIM control). Also, IM-NoGC (IM control, comprising both IIM and CIM Control) was compared with healthy gastric mucosa. Differentially expressed genes were obtained and functional analyses (GSEA and IPA softwares) were performed. Some deregulated genes were validated by qPCR. Results: Histological subtypes of intestinal metaplasia that progress or not to GC differ less among them than to healthy mucosa. Incomplete intestinal metaplasia has a higher number of over-expressed carcinogenic genes and molecular processes than the complete subtype. Most relevant molecular processes and genes in this group include antigenic processing, inflammation, activation of cell cycle and cell proliferation, oncogenes and tumor suppressors. When IM-NoGC is compared with healthy gastric mucosa new identified transcripts include TRIM, TMEM, homeobox, transporters and nucleolar RNAs SNORDs116. We confirm previously reported processes such us intestinal differentiation, metabolism of lipids and of xenobiotics and identify new ones such as non tumoral Warburg effect and melatonin degradation. Conclusions: Differentially expressed genes and molecular processes have been identified for the first time in intestinal metaplasia that progress to gastric cancer. New genes and molecular processes have also been identified in intestinal metaplasia in comparison with healthy gastric mucosa.

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Single-cell atlas of lineage states, tumor microenvironment and subtype specific expression programs in gastric cancer

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