山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (5): 43-49.doi: 10.6040/j.issn.1671-7554.0.2022.0121
高惠茹1,2,杜甜甜1,2,王允山1,2,杜鲁涛1,2,王传新1,2
GAO Huiru1,2, DU Tiantian1,2, WANG Yunshan1,2, DU Lutao1,2, WANG Chuanxin1,2
摘要: 目的 探究胃癌及胃正常组织的细胞组成,分析调节性T细胞在胃癌及胃正常组织中的差异。 方法 下载胃癌单细胞转录组测序数据并进行质控、降维聚类及细胞注释,提取调节性T细胞进行差异基因、轨迹、GSVA及细胞相互作用分析,明确正常组织和肿瘤组织来源的调节性T细胞特征。 结果 在细胞组成方面,不同患者、不同样本类型之间存在较大异质性。与正常组织相比,调节性T细胞在肿瘤组织占比更高,与细胞死亡、细胞周期等通路相关。细胞相互作用分析显示,肿瘤组织中调节性T细胞与其他细胞相互作用频率更低、强度更大,互作模式具有显著变化。 结论 调节性T细胞主要在胃癌肿瘤微环境中存在。胃癌及胃正常组织中调节性T细胞在数量、功能等方面存在显著差异。
中图分类号:
[1] Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer [J]. Gastroenterology, 2020, 159(1): 335-349. [2] 曹毛毛, 李贺, 孙殿钦, 等. 2000-2019年中国胃癌流行病学趋势分析[J]. 中华消化外科杂志, 2021, 20(1): 102-109. CAO Maomao, LI He, SUN Dianqin, et al. Epidemiological trend analysis of gastric cancer in China from 2000 to 2019 [J]. Chinese Journal of Digestive Surgery, 2021, 20(1): 102-109. [3] Fan J, Slowikowski K, Zhang F. Single-cell transcriptomics in cancer: computational challenges and opportunities [J]. Exp Mol Med, 2020, 52(9): 1452-1465. [4] Ding S, Chen X, Shen K. Single-cell RNA sequencing in breast cancer: understanding tumor heterogeneity and paving roads to individualized therapy [J]. Cancer Commun(Lond), 2020, 40(8): 329-344. [5] Qi Z, Barrett T, Parikh AS, et al. Single-cell sequencing and its applications in head and neck cancer [J]. Oral Oncol, 2019, 99: 104441. doi: 10.1016/j.oraloncology.2019.104441. [6] Tieng FYF, Baharudin R, Abu N, et al. Single cell transcriptome in colorectal cancer-current updates on its application in metastasis, chemoresistance and the roles of circulating tumor cells [J]. Front Pharmacol, 2020, 11: 135. doi: 10.3389/fphar.2020.00135. [7] 包梦颖, 曾燕玉, 代艳, 等. 基于单细胞RNA测序探讨膀胱癌患者外周血单个核细胞特征的研究[J]. 广西医科大学学报, 2021, 38(3): 636-643. BAO Mengying, ZENG Yanyu, DAI Yan, et al. Study on the characteristics of peripheral blood mononuclear cells in bladder cancer patients by single cell RNA sequencing [J]. Journal of Guangxi Medical University, 2021, 38(3): 636-643. [8] Luo Q, Fu Q, Zhang X, et al. Application of single-cell RNA sequencing in pancreatic cancer and the endocrine pancreas [J]. Adv Exp Med Biol, 2020, 1255: 143-152. doi: 10.1007/978-981-15-4494-1_12. [9] Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy [J]. Cell Res, 2017, 27(1): 109-118. [10] Whiteside TL. What are regulatory T cells(Treg)regulating in cancer and why? [J]. Semin Cancer Biol, 2012, 22(4): 327-334. [11] Sathe A, Grimes SM, Lau BT, et al. Single-cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment [J]. Clin Cancer Res, 2020, 26(11): 2640-2653. [12] Zhang M, Hu S, Min M, et al. Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing [J]. Gut, 2021, 70(3):464-475. [13] Zhang P, Yang M, Zhang Y, et al. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer [J]. Cell Rep, 2019, 27(6): 1934-1947. [14] Bassez A, Vos H, Van Dyck L, et al. A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer [J]. Nat Med, 2021, 27(5): 820-832. [15] Zheng L, Qin S, Si W, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells [J]. Science, 2021, 374(6574): abe6474. doi: 10.1126/science.abe6474. [16] Jin S, Guerrero-Juarez CF, Zhang L, et al. Inference and analysis of cell-cell communication using CellChat [J]. Nat Commun, 2021, 12(1): 1088. doi: 10.1038/s41467-021-21246-9. [17] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2018, 68(6): 394-424. [18] Xie M, Wei J, Xu J. Inducers, attractors and modulators of CD4(+)Treg cells in non-small-cell lung cancer [J]. Front Immunol, 2020, 11: 676. doi: 10.3389/fimmu.2020.00676. [19] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation [J]. Cell, 2011, 144(5): 646-674. [20] Kumar V, Ramnarayanan K, Sundar R, et al. Single-cell atlas of lineage states, tumor microenvironment and subtype-specific expression programs in gastric cancer [J]. Cancer Discov, 2022, 12(3): 670-691. [21] Tanaka A, Sakaguchi S. Targeting Treg cells in cancer immunotherapy [J]. Eur J Immunol, 2019, 49(8): 1140-1146. [22] Ahmadzadeh M, Pasetto A, Jia L, et al. Tumor-infiltrating human CD4(+)regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity [J]. Sci Immunol, 2019, 4(31): eaao4310. doi: 10.1126/sciimmunol.aao4310. [23] 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. [24] Marzagalli M, Ebelt ND, Manuel ER. Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment [J]. Semin Cancer Biol, 2019, 59: 236-250. doi: 10.1016/j.semcancer.2019.08.002. [25] Kamiya T, Seow SV, Wong D, et al. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells [J]. J Clin Invest, 2019, 129(5): 2094-2106. [26] Prasnikar E, Perdih A, Borisek J. All-atom simulations reveal a key interaction network in the HLA-E/NKG2A/CD94 immune complex fine-tuned by the nonameric peptide [J]. J Chem Inf Model, 2021, 61(7): 3593-3603. [27] Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity [J]. Proc Natl Acad Sci U S A, 2009, 106(42): 17858-17863. [28] Mathewson ND, Ashenberg O, Tirosh I, et al. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis [J]. Cell, 2021, 184(5): 1281-1298. |
[1] | 付佳,王路路,胡帅,陈哲平,刘东义,李青松,卢国栋,张贺,赵鑫,冯昌. 不同入路腰方肌阻滞对胃癌根治患者术后恢复的影响[J]. 山东大学学报 (医学版), 2022, 60(8): 50-57. |
[2] | 王景,谢艳,李培龙,杜鲁涛,王传新. GZMB基因cg16212145位点的异常甲基化芯片测定对胃癌早筛的价值[J]. 山东大学学报 (医学版), 2022, 60(6): 26-34. |
[3] | 包舒晴,杨明月,刘端瑞,汪运山,郏雁飞. NOX4在幽门螺旋杆菌诱导胃癌细胞ROS中的作用[J]. 山东大学学报 (医学版), 2022, 60(6): 19-25. |
[4] | 穆彦熹,汪文杰,陈康,姚亚龙,李金洲,魏浩旗,刘海鹏,黄泽平,陈晓. 探寻一家系短期3例胃癌的临床病理及其相关肿瘤特征[J]. 山东大学学报 (医学版), 2022, 60(11): 96-101. |
[5] | 马燕燕,龚瑶琴. 人脑类器官在神经发育疾病研究中的应用[J]. 山东大学学报 (医学版), 2021, 59(9): 22-29. |
[6] | 褚晏,刘端瑞,朱文帅,樊荣,马晓丽,汪运山,郏雁飞. DNA甲基化转移酶在胃癌中的表达及其临床意义[J]. 山东大学学报 (医学版), 2021, 59(7): 1-9. |
[7] | 罗兵. EB病毒对胃癌表观遗传学的影响[J]. 山东大学学报 (医学版), 2021, 59(5): 30-39. |
[8] | 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 1(7): 47-52. |
[9] | 支梦伟,江志伟,戴新娟,王刚,程伟. 加速康复外科指导下胃癌患者围手术期心率变异度的临床观察[J]. 山东大学学报 (医学版), 2020, 58(11): 85-91. |
[10] | 王亚杰,闻蓓,施浩宇,商亮,董康迪,李乐平. 胃癌合并轻型血友病术后出血1例[J]. 山东大学学报 (医学版), 2020, 58(1): 91-93. |
[11] | 房鹏,王刚,赵健,刘江,王海锋,周嘉晖,江志伟. 加速康复外科减少胃癌患者术后重症监护病房住院时间的临床观察[J]. 山东大学学报 (医学版), 2019, 57(9): 28-32. |
[12] | 赵鸿渐,周继军,苏庆亮,赵硕,李玉明. 胃癌间充质干细胞与SGC-7901荷瘤鼠肿瘤进展的相关性[J]. 山东大学学报 (医学版), 2019, 57(9): 69-73. |
[13] | 李乐平,崔怀平,商亮. 加速康复外科在胃肠外科手术中的应用[J]. 山东大学学报 (医学版), 2019, 57(9): 5-11. |
[14] | 董昌正,周伟,李风周,臧义丰,丁印鲁. 全腹腔镜下全胃+胆囊+阑尾切除经自然腔道取标本手术1例[J]. 山东大学学报 (医学版), 2019, 57(7): 122-124. |
[15] | 周伟,董昌正,臧义丰,丁印鲁. 单孔加一孔腹腔镜胃癌根治+UncutRoux-en-Y吻合手术1例[J]. 山东大学学报 (医学版), 2019, 57(11): 118-120. |
|