دورية أكاديمية
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Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

التفاصيل البيبلوغرافية
العنوان: Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.
المؤلفون: Ma R; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Zhou X; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China., Zhai X; Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Wang C; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Hu R; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Chen Y; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Shi L; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China., Fang X; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou, China., Liao Y; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Ma L; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Jiang M; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China., Wu J; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China., Wang R; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Chen J; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China., Cao T; Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Du G; Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Zhao Y; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Wu W; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Chen H; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China., Li S; Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Lian Q; Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.; Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China., Guo G; Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.; Institute of Hematology, Zhejiang University, Hangzhou, China., Xiao J; Department of Medical Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China., Hutchins AP; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China., Yuan P; Guangdong Institute of Gastroenterology, Guangzhou, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.; Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
المصدر: Cell proliferation [Cell Prolif] 2024 May; Vol. 57 (5), pp. e13591. Date of Electronic Publication: 2024 Feb 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications Country of Publication: England NLM ID: 9105195 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2184 (Electronic) Linking ISSN: 09607722 NLM ISO Abbreviation: Cell Prolif Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Oxford, England] : Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications, 1991-
مواضيع طبية MeSH: Stomach Neoplasms*/immunology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/pathology , Stomach Neoplasms*/blood , Leukocytes, Mononuclear*/metabolism , Leukocytes, Mononuclear*/immunology , Single-Cell Analysis* , Sequence Analysis, RNA*, Humans ; Neutrophils/metabolism ; Neutrophils/immunology ; Male ; Female ; Middle Aged ; Signal Transduction ; Aged ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
مستخلص: Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.
(© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 2020B1111170004 Guangdong Provincial Clinical Research Center for Digestive Diseases; JCYJ20200109141018712 Shenzhen Innovation Committee of Science and Technology; RCBS20221008093109033 Shenzhen Science and Technology Innovation Commission; 31930028 National Natural Science Foundation of China; 31970674 National Natural Science Foundation of China; 32150710521 National Natural Science Foundation of China; 32270597 National Natural Science Foundation of China; National Key Clinical Discipline; LTGC23C070002 Zhejiang Provincial Natural Science Foundation of China; 2022JBGS13 The key project funding in the Sixth Affiliated Hospital, Sun Yat-sen University
تواريخ الأحداث: Date Created: 20240206 Date Completed: 20240429 Latest Revision: 20240501
رمز التحديث: 20240501
مُعرف محوري في PubMed: PMC11056698
DOI: 10.1111/cpr.13591
PMID: 38319150
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2184
DOI:10.1111/cpr.13591