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SCI-E Article

Single-cell analysis of gastric pre-cancerous and cancer lesions reveals cell lineage diversity and intratumoral heterogeneity

	성명	조수영 ()
	소속	과학기술융합대학 분자생명과학과
	캠퍼스
	우수선정주	2022년 02월 3째주

Author

조수영 (Dept Mol & Life Sci) corresponding author;

Corresponding Author Info

Cho, SY (corresponding author), Natl Canc Ctr, 323 Ilsan Ro, Goyang Si 10408, Gyeonggi Do, South Korea.; Nam, KT (corresponding author), Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Brain Korea 21 PLUS Project Med Sci, Seoul 03722, South Korea.; Lee,

E-mail

sooycho@hanyang.ac.kr

Document Type

Article

Source

NPJ PRECISION ONCOLOGY Volume:6 Issue:1 Pages:- Published:2022

Times Cited

External Information

http://dx.doi.org/10.1038/s41698-022-00251-1

Abstract

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

Web of Science Categories

Oncology

Funding

National Research Foundation of Korea (NRF) - Korean government (MSIT) [NRF-2018R1C1B6001475, NRF-2019R1A2C1003401, NRF-2021R1A2C1009415]; National Cancer Center Grant [1711290, 2110050]

Language

English

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