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Relationships of tumor diferentiation and immune infltration in gastric cancers revealed by single‑cell RNA‑seq analyses
Xin Zhou1,5; Jingwei Yang1,2; Yongqu Lu1,5,8; Yanpeng Ma5; Yan Meng5; Qingqing Li1,2; Junpeng Gao1,2; Zhaoyu Jiang5; Limei Guo7; Wei Wang1,2; Yun Liu1,2,4; Lu Wen1,3; Miao Kai6; Wei Fu1,5; Fuchou Tang1,2,3,4
2023-02-02
Source PublicationCELLULAR AND MOLECULAR LIFE SCIENCES
ISSN1420-682X
Volume80Pages:57
Abstract

Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial–mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8+ T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8+ cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and NEC were systematically revealed, which may partially explain the strong tumor heterogeneities of gastric cancer. Especially along the DGC to NEC trans-differentiation path, immune-evasion was gradually enhanced with the decreasing activities of interferon pathway responses in malignant cells.

KeywordIntra-tumor Heterogeneity Pathological Phenotype Tumor Immune Microenvironment
DOI10.1007/s00018-023-04702-1
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000924831900001
PublisherSPRINGER BASEL AG, PICASSOPLATZ 4, BASEL 4052, SWITZERLAND
Scopus ID2-s2.0-85147318602
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionFaculty of Health Sciences
Cancer Centre
DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorWei Fu; Fuchou Tang
Affiliation1.School of Life Sciences, Biomedical Pioneering Innovation Center, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, People’s Republic of China
2.Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Diferentiation, Beijing 100871, People’s Republic of China
3.Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, People’s Republic of China
4.Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, People’s Republic of China
5.Peking University Third Hospital Cancer Center, Beijing, 100191, People’s Republic of China
6.Faculty of Health Sciences, Cancer Center, University of Macau, Macau SAR, People’s Republic of China
7.Department of Pathology, School of Basic Medical Science, Peking University Third Hospital, Peking University Health Science Center, Beijing, 100191, People’s Republic of China
8.Department of Breast and Thyroid Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China
Recommended Citation
GB/T 7714
Xin Zhou,Jingwei Yang,Yongqu Lu,et al. Relationships of tumor diferentiation and immune infltration in gastric cancers revealed by single‑cell RNA‑seq analyses[J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2023, 80, 57.
APA Xin Zhou., Jingwei Yang., Yongqu Lu., Yanpeng Ma., Yan Meng., Qingqing Li., Junpeng Gao., Zhaoyu Jiang., Limei Guo., Wei Wang., Yun Liu., Lu Wen., Miao Kai., Wei Fu., & Fuchou Tang (2023). Relationships of tumor diferentiation and immune infltration in gastric cancers revealed by single‑cell RNA‑seq analyses. CELLULAR AND MOLECULAR LIFE SCIENCES, 80, 57.
MLA Xin Zhou,et al."Relationships of tumor diferentiation and immune infltration in gastric cancers revealed by single‑cell RNA‑seq analyses".CELLULAR AND MOLECULAR LIFE SCIENCES 80(2023):57.
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