|本期目录/Table of Contents|

[1]胡逸恺,宋明坤,王旭东,等.单细胞转录组探究胃癌转移过程中MHC-Ⅱ类分子的演进缺失[J].天津医科大学学报,2023,29(01):1-8.
 HU Yi-kai,SONG Ming-kun,WANG Xu-dong,et al.Single-cell transcriptome analysis revealed the evolutionary deletion of MHC-Ⅱ expression in gastric cancer metastasis[J].Journal of Tianjin Medical University,2023,29(01):1-8.
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单细胞转录组探究胃癌转移过程中MHC-Ⅱ类分子的演进缺失(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
29卷
期数:
2023年01期
页码:
1-8
栏目:
肿瘤基础研究专题
出版日期:
2023-01-20

文章信息/Info

Title:
Single-cell transcriptome analysis revealed the evolutionary deletion of MHC-Ⅱ expression in gastric cancer metastasis
文章编号:
1006-8147(2023)01-0001-08
作者:
胡逸恺12宋明坤2王旭东1姬倩颖1李龙2
(1.天津医科大学第二临床医学院2018级临床医学专业,天津300070;2.天津医科大学基础医学院免疫学系,天津300070)
Author(s):
HU Yi-kai12SONG Ming-kun2WANG Xu-dong1JI Qian-ying1LI Long2
(1.Class of 2018,Clinical Medicine,Second School of Clinical Medicine,Tianjin 300070,China;2.Department of Immunology,School of Basic Medical Science,Tianjin Medical University,Tianjin 300070,China)
关键词:
胃癌单细胞分析单细胞RNA测序TAMSPP1MHC-Ⅱ
Keywords:
stomach neoplasmssingle-cell analysissingle-cell RNA-seqTAMSPP1MHC-Ⅱ
分类号:
R392.9
DOI:
-
文献标志码:
A
摘要:
目的:使用单细胞转录组数据绘制胃癌免疫微环境组成图谱,探究胃癌转移过程中MHC-Ⅱ类分子演进缺失的免疫机制。方法:在GEO数据库中获取胃癌原发癌和转移癌单细胞数据集,基于R(4.1.2)、Python(3.7),对该数据集进行分群、拷贝数变异(CNV)、拟时序、基因集变异(GSVA)分析、转录因子分析、非负矩阵分解、免疫细胞细分亚群和基因集富集分析,并结合来自TCGA等数据库的多个公共转录组数据集,验证所得出的结论。结果:拟时序分析反映MHC-Ⅱ类分子在癌症转移过程中演进缺失,转录因子分析观察到IRF1、STAT1等转录因子在原发癌中的高表达,非负矩阵分解探查到原发癌中独有的干扰素(IFN)γ表达模块,但原发癌展现了较冷的免疫微环境。免疫细胞的亚群分类展示了树突状细胞、巨噬细胞、T细胞等在微环境中的分布。细胞通讯分析显示MDSC样和SPP1+肿瘤相关巨噬细胞(TAM)抑制了转移癌中IFNγ的分泌并表现了促血管生成活性。基于这两种TAM的生物标志构建的评分在胃癌中具有预后意义(Log-Rank P<0.05)。scPAGE在较大规模的bulk转录组层面对单细胞分析获得的结果进行了验证。结论:TAM介导IFNγ分泌抑制,其在转移癌较原发癌中分泌相对较少,是MHC-Ⅱ在两者间表达出现差异的原因之一。针对MDSC样 TAM和SPP1+ TAM的研究可能是肿瘤免疫治疗的另一突破点。
Abstract:
Objective: To depict the immune microenvironment atlas of gastric cancer and to explore the immune mechanism under the evolutionary deletion of MHC-Ⅱ expression in gastric cancer metastasis with single-cell transcriptome data. Methods:A single-cell data set of primary and metastatic gastric cancer was obtained from the Gene Expression Omnibus(GEO) database,combined with multiple datasets like TCGA. With R(4.1.2) and Python(3.7),clustering,copy number variation(CNV) analysis,pseudotime analysis,gene set variation analysis(GSVA),transcription factor analysis,consensus non-negative matrix factorization analysis,immune cell subpopulation analysis and gene set enrichment analysis were conducted. Combined with multiple public transcriptome data sets from TCGA and other databases,the conclusions were verified. Results:The depleted expression of MHC-Ⅱ in metastatic cancer was observed by pseudotime analysis,while a high expression of IRF1 and STAT1 in primary carcinoma was observed by transcription factor analysis. Consensus Non-negative Matrix Factorization obtained a unique IFNγ expression module from the primary tumor,but a colder immune microenvironment was observed in primary tumor. Immune cell subpopulation analysis reveals the distribution of dendritic cells,macrophages and T cells in the tumor microenvironment. Cell chat analysis shows that MDSC-like and SPP1+ Tumor-associated Macrophages(TAM) were found to play a crucial part in angiogenesis. The score constructed on the basis of TAMs′ biomarkers shows prognostic significance in gastric cancer (Log-Rank P<0.05). ScPAGE verified the results of single cell analysis at the bulk transcriptome level. Conclusion:The inhibition of IFNγ emission mediated by TAM in metastatic tumor may contribute to the difference of MHC-Ⅱ expression between the primary and metastatic sites. Research on MDSC-like and SPP1+ TAM may become another breakthrough point of tumor immunotherapy.

参考文献/References:

[1] SEENEEVASSEN L,BESS?魬DE E,M?魪GRAUD F,et al. Gastric cancer:advances in carcinogenesis research and new therapeutic strategies[J]. Int J Mol Sci,2021,22(7):3418.
[2] LAWSON D A,KESSENBROCK K,DAVIS R T,et al. Tumour heterogeneity and metastasis at single-cell resolution[J]. Nat Cell Biol,2018,20(12):1349-1360.
[3] JIANG H,YU D,YANG P,et al. Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing[J]. Clin Transl Med,2022,12(2):e730.
[4] WANG B,ZHANG Y,QING T,et al. Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq[J]. Sci Rep,2021,11(1):1141.
[5] CHEN F,ZHANG Y,VARAMBALLY S,et al. Molecular correlates of metastasis by systematic pan-cancer analysis across the cancer genome atlas[J]. Mol Cancer Res,2019,17(2):476-487.
[6] GULATI G S,SIKANDAR S S,WESCHE D J,et al. Single-cell transcriptional diversity is a hallmark of developmental potential[J]. Science,2020,367(6476):405-411.
[7] BAGAEV A,KOTLOV N,NOMIE K,et al. Conserved pan-cancer microenvironment subtypes predict response to immunotherapy[J]. Cancer Cell,2021,39(6):845-865.e7.
[8] CHEN Y,YIN J,LI W,et al. Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma[J]. Cell Res,2020,30(11):1024-1042.
[9] GUO X,ZHANG Y,ZHENG L,et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing[J]. Nat Med,2018,24(7):978-985.
[10] LIU Y,ZHANG Q,XING B,et al. Immune phenotypic linkage between colorectal cancer and liver metastasis[J]. Cancer Cell,2022, 40(4):424-437.e5.
[11] REN X,ZHANG L,ZHANG Y,et al. Insights gained from single-cell analysis of immune cells in the tumor microenvironment[J]. Annu Rev Immunol,2021,39:583-609.
[12] ELYADA E,BOLISETTY M,LAISE P,et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts[J]. Cancer Discov,2019,9(8): 1102-1123.
[13] NURMIK M,ULLMANN P,RODRIGUEZ F,et al. In search of definitions:cancer-associated fibroblasts and their markers[J]. Int J Cancer,2020,146(4):895-905.
[14] MAIER B,LEADER A M,CHEN S T,et al. A conserved dendritic-cell regulatory program limits antitumour immunity[J]. Nature,2020, 580(7802):257-262.
[15] WANG R,ZHENG X,WANG J,et al. Improving bulk RNA-seq classification by transferring gene signature from single cells in acute myeloid leukemia[J]. Brief Bioinform,2022,23(2) :bbac002.
[16] 韩小孩,张耀辉,孙福军,等. 基于主成分分析的指标权重确定方法[J]. 四川兵工学报,2012,33(10):124-126.
[17] ZHOU H,TANG Y,ZHENG C. Revisiting IRF1-mediated antiviral innate immunity[J]. Cytokine Growth Factor Rev,2022,64:1-6.
[18] ADHIKARI A,COBB B,EDDINGTON S,et al. IFN-γ and CIITA modulate IL-6 expression in skeletal muscle[J]. Cytokine X,2020,2(2):100023.
[19] CORRY J,MOTT H R,OWEN D. Activation of STAT transcription factors by the Rho-family GTPases[J]. Biochem Soc Trans,2020, 48(5):2213-2227.
[20] ITO N,TSUJIMOTO H,UENO H,et al. Helicobacter pylori-mediated immunity and signaling transduction in gastric cancer[J]. J Clin Med,2020,9(11) :3699.
[21] ONSTENK W,SIEUWERTS A M,MOSTERT B,et al. Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer[J]. Oncotarget,2016,7(37):59058-59069.
[22] SCHMIDT A,ARMENTO A,BUSSOLATI O,et al. Hepatoblastoma:glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival[J]. J Cancer Res Clin Oncol,2021,147(11):3169-3181.
[23] KEMP S B,CARPENTER E S,STEELE N G,et al. Apolipoprotein E promotes immune suppression in pancreatic cancer through NF-κB-mediated production of CXCL1[J]. Cancer Res,2021,81(16):4305-4318.
[24] GAO J,SHI L Z,ZHAO H,et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy[J]. Cell,2016,167(2):397-404.e9.
[25] IVASHKIV L B. IFNγ:signalling,epigenetics and roles in immunity,metabolism,disease and cancer immunotherapy[J]. Nat Rev Immunol,2018,18(9):545-558.
[26] CHENG S,LI Z,GAO R,et al.A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells[J].Cell,2021,184(3):792-809.

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备注/Memo

备注/Memo:
基金项目:天津市高等学校大学生创新创业训练计划(202010062016)
作者简介:胡逸恺(2001-),男,学士在读,研究方向:肿瘤免疫;通信作者:李龙,E-mail:Long.Li@tmu.edu.cn。
更新日期/Last Update: 2023-02-01