基于单细胞测序解析四君子汤加减对结直肠癌化疗患者肿瘤微环境的影响  

Effect of modified Sijunzi decoction on tumor microenvironment in patients with colorectal cancer chemotherapy based on single⁃cell sequencing

作　　者：肖国中 贺秋兰[4] 刘访 陈华显[1,2,3] 万星阳 任东林[1,2,3] 林宏城 XIAO Guozhong;HE Qiulan;LIU Fang;CHEN Huaxian;Huaxian;WAN Xingyang;REN Donglin;LIN Hongcheng(Department of Colorectal Surgery,The Sixth Affiliated Hospital,SunYat-sen University,Guangzhou 510655,China;Department of General Surgery,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,Guangzhou 510655,China;不详)

机构地区：[1]中山大学附属第六医院肛肠外科,广州510655 [2]中山大学附属第六医院普通外科,广州510655 [3]广东省结直肠盆底疾病研究重点实验室,广州510655 [4]中山大学附属第一医院麻醉科,广州510080 [5]贵州中医药大学第一附属医院,贵阳550001

出　　处：《实用医学杂志》2023年第10期1296-1304,共9页The Journal of Practical Medicine

基　　金：国家自然科学基金面上项目(编号:81973847,82174369);国家自然科学基金青年科学基金项目(编号:82004368);广东省自然科学基金面上项目(编号:2020A1515011254);广东自然科学基金杰出青年项目(编号:2022B1515020003);深圳华大生命科学研究院开放基金项目(编号:BGIRSZ20210005)。

摘　　要：目的探究四君子汤加减辅助化疗治疗结直肠癌的临床疗效及其对化疗患者肿瘤微环境的影响。方法回顾性分析30例结直肠癌化疗患者的临床资料,按照化疗期间是否服用过四君子汤加减分为两组,服用过四君子汤者为联合治疗组,未服用者为对照组。并对同一患者治疗前后配对的肿瘤组织进行单细胞RNA测序分析。结果联合治疗组与对照组分别纳入15例患者,两组患者的性别构成、年龄、结直肠癌分期、分化程度比较差异无统计学意义(P>0.05)。治疗后,联合治疗组食少纳呆(P<0.05)、神疲乏力(P<0.05)、腹胀(P<0.05)、便溏(P<0.05)的中医证候评分均低于对照组,差异有统计学意义。通过单细胞测序数据分析发现,与对照组相比,治疗后联合治疗组CD8+T细胞比例更高,而且联合治疗组CD8+T细胞的TNF⁃α/NF⁃κB信号通路、IL6/JAK/STAT3信号通路、IL2/STAT5信号通路激活。此外,两组效应T细胞的差异基因比较显示,联合治疗组的效应T细胞在治疗后LTB、IL7R等基因高表达。效应T细胞在联合治疗组功能被激活,可能与TNF⁃α/NF⁃κB通路和IL2/STAT5通路活性增高有关。最后,四君子汤加减可能还通过激活巨噬细胞吞噬功能及促进巨噬细胞与效应T细胞的细胞互作发挥潜在治疗作用。结论四君子汤加减在结直肠癌化疗患者的治疗中有效,可显著改善患者生活质量。四君子汤加减对结直肠癌化疗患者的肿瘤微环境有显著影响,其可能通过增强效应T细胞功能和增强巨噬细胞抗肿瘤免疫活性发挥作用。Objective To explore the clinical curative effect of modified Sijunzi decoction on adjuvant che⁃motherapy for colorectal cancer and its effect on the tumor microenvironment of patients receiving chemotherapy.Methods The clinical data of 30 patients with colorectal cancer who received chemotherapy were retrospectively analyzed.They were divided into combined treatment group and control group according to whether they took Sijunzi decoction during chemotherapy.Single⁃cell RNA⁃sequencing of paired tumor tissues from the same patient before and after treatment was performed.Results Fifteen patients were included in the combined treatment group and the control group,respectively.There was no statistically significant difference between the two groups in terms of gender composition,age,colorectal cancer stage,and differentiation.After treatment,the TCM symptom scores of anorexia(P<0.05),loss of spirit(P<0.05),abdominal distension(P<0.05)and loose stools(P<0.05)in the combined treatment group were lower than those of the control group,and the differences were statistically significant.Analysis of single⁃cell sequencing data revealed that the proportion of CD8+T cells was higher in the combined treatment group after treatment compared with the control group,and the TNF⁃α/NF⁃kB signaling path⁃way,IL6/JAK/STAT3 signaling pathway,and IL2/STAT5 signaling were activated in CD8+T cells in the combined treatment group.In addition,comparison of differential genes of effector T cells in the two groups showed that effector T cells in the combined treatment group highly expressed genes such as LTB and IL7R after treatment.The effector T cell function was activated in the combination treatment group,which may be related to the increased activity of TNF⁃α/NF⁃kB pathway and IL2/STAT5 pathway.Finally,modified Sijunzi decoction may also play a potential therapeutic role by activating macrophage phagocytosis and promoting cellular interactions between macrophages and effector T cells.Conclusion Modified Sijunzi decoct

关 键 词：结直肠癌 四君子汤加减 单细胞测序 肿瘤微环境 

分 类 号：R735[医药卫生—肿瘤]