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

Authors
 Jihyun Kim  ;  Charny Park  ;  Kwang H Kim  ;  Eun Hye Kim  ;  Hyunki Kim  ;  Jong Kyu Woo  ;  Je Kyung Seong  ;  Ki Taek Nam  ;  Yong Chan Lee  ;  Soo Young Cho 
Citation
 NPJ PRECISION ONCOLOGY, Vol.6(1) : 9, 2022-01 
Journal Title
NPJ PRECISION ONCOLOGY
Issue Date
2022-01
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.
Files in This Item:
T202200468.pdf Download
DOI
10.1038/s41698-022-00251-1
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kwang Hui(김광휘)
Kim, Eun Hye(김은혜) ORCID logo https://orcid.org/0000-0001-6691-6837
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Nam, Ki Taek(남기택)
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188025
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