Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing.

Gut
Min ZhangYan Liu

Abstract

Tumour heterogeneity represents a major obstacle to accurate diagnosis and treatment in gastric adenocarcinoma (GA). Here, we report a systematic transcriptional atlas to delineate molecular and cellular heterogeneity in GA using single-cell RNA sequencing (scRNA-seq). We performed unbiased transcriptome-wide scRNA-seq analysis on 27 677 cells from 9 tumour and 3 non-tumour samples. Analysis results were validated using large-scale histological assays and bulk transcriptomic datasets. Our integrative analysis of tumour cells identified five cell subgroups with distinct expression profiles. A panel of differentiation-related genes reveals a high diversity of differentiation degrees within and between tumours. Low differentiation degrees can predict poor prognosis in GA. Among them, three subgroups exhibited different differentiation grade which corresponded well to histopathological features of Lauren's subtypes. Interestingly, the other two subgroups displayed unique transcriptome features. One subgroup expressing chief-cell markers (eg, LIPF and PGC) and RNF43 with Wnt/β-catenin signalling pathway activated is consistent with the previously described entity fundic gland-type GA (chief cell-predominant, GA-FG-CCP). We further c...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Lornella SeeneevassenChristine Varon
Jun 11, 2021·Journal of Hematology & Oncology·Yalan LeiSi Shi
May 25, 2021·Molecular Therapy Oncolytics·Guangshun SunYangbai Sun
Jul 6, 2021·Frontiers in Genetics·Rebecca J HertzmanElizabeth J Phillips
Aug 28, 2021·Biomolecules·Gabriel DoradoPilar Hernández
Aug 16, 2021·Gastroenterology·Daisuke DouchiYoshiaki Ito
Feb 28, 2021·Annual Review of Immunology·Xianwen RenZemin Zhang
Aug 14, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hye Young JeongHoon Hur

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Methods Mentioned

BETA
dissection
genotyping
biopsy
biopsies
scRNA-seq

Software Mentioned

Metascape
Monocle pseudotime trajectory analysis
GSEA
Monocle

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