[1]李爱丽,魏宏英,高先凤.晚期胃癌患者外周血单个核细胞中AIM2的表达及其与肠道菌群和靶向治疗疗效的关系研究[J].现代检验医学杂志,2025,40(02):6-10.[doi:10.3969/j.issn.1671-7414.2025.02.002]
　LI Aili,WEI Hongying,GAO Xianfeng.Study on the Expression of AIM2 in PBMC of Patients with Advanced Gastric Cancer and Its Relationship with Intestinal Microbiota and the Efficacy of Targeted Therapy[J].Journal of Modern Laboratory Medicine,2025,40(02):6-10.[doi:10.3969/j.issn.1671-7414.2025.02.002]
点击复制

晚期胃癌患者外周血单个核细胞中AIM2的表达及其与肠道菌群和靶向治疗疗效的关系研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
6-10
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Study on the Expression of AIM2 in PBMC of Patients with Advanced Gastric Cancer and Its Relationship with Intestinal Microbiota and the Efficacy of Targeted Therapy
文章编号:
1671-7414（2025）02-006-05
作者:
李爱丽; 魏宏英; 高先凤
（国药同煤总医院肿瘤内科，山西大同 037003）
Author(s):
LI Aili; WEI Hongying; GAO Xianfeng
(Department of Oncology，Sinopharm Tongmei General Hospital， Shanxi Datong 037003，China)
关键词:
晚期胃癌; 黑素瘤缺乏因子2; 肠道菌群; 靶向治疗
分类号:
R735.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.002
文献标志码:
A
摘要:
目的 探讨晚期胃癌（GC）患者外周血单个核细胞（PBMC）中黑素瘤缺乏因子2（AIM2）基因表达及其与肠道菌群和靶向治疗疗效的关系。方法 选取2023 年1 ～ 12 月收治的83 例晚期GC 患者，均给予曲妥珠单抗/ 纳武利尤单抗联合常规化疗治疗，4 周/ 疗程，持续治疗3 个疗程，评价靶向治疗疗效。利用16S rDNA 测序技术检测患者肠道菌群丰度；实时荧光定量PCR（qRT-PCR）检测PBMC 中AIM2 mRNA 表达水平，按其中位数分为高表达组和低表达组；采用Pearson 相关性分析AIM2 表达与肠道菌群相对丰度、靶向治疗疗效及临床特征的关系。结果 在门水平上，AIM2高表达组拟杆菌门（0.70±0.15）和变形菌门（0.71±0.21）相对丰度明显低于低表达组（0.81±0.17，0.80±0.16），厚壁菌门（0.73±0.12）相对丰度明显高于低表达组（0.64±0.08），差异具有统计学意义（t=3.108，2.210，4.061，均 P＜ 0.05）；在属水平上，AIM2 高表达组拟杆菌属（0.13±0.02）相对丰度明显低于低表达组（0.19±0.04），肠球菌属（0.31±0.08）和大肠埃希菌属（0.18±0.04）相对丰度明显高于低表达组（0.12±0.05，0.10±0.02），差异具有统计学意义（t=8.472，15.462，11.722，均 P ＜ 0.05）。Pearson 相关分析显示，门水平上，AIM2 表达与厚壁菌门相对丰度呈正相关（r=0.598，P ＜ 0.05），与拟杆菌门和变形菌门相对丰度呈负相关（r=-0.641，-0.520，均 P ＜ 0.05）；属水平上，AIM2 表达与肠球菌属和大肠埃希菌属相对丰度呈正相关（r=0.529，0.577，均 P ＜ 0.05），与拟杆菌属相对丰度呈负相关（r= -0.574，P ＜ 0.05）。83 例晚期GC 患者中靶向治疗有效17 例，靶向治疗无效66 例，总客观缓解率（ORR）为20.48%；AIM2 高表达组病灶直径（5.73±0.74cm）和cTNM分期IV 期占比（53.85%）显著低于低表达组（6.08±0.51cm，75.00%），靶向治疗ORR（30.77%）高于低表达组（11.36%），差异具有统计学意义（t/χ2/Z=2.477，6.558，4.780，均P ＜ 0.05）。结论 晚期GC 患者PBMC 中AIM2 表达与患者肠道菌群失调及靶向治疗效果密切相关，检测AIM2 表达有利于指导临床筛选出对靶向治疗受益的患者。
Abstract:
Objective To investigate the relationship between the expression of absent in melanoma 2(AIM2) gene in peripheral blood peripheral blood mononuclear cell (PBMC) of patients with advanced gastric cancer (GC) and the intestinal flora and the efficacy of targeted therapy. Methods 83 patients with advanced GC who were treated from January to December 2023 were all given Trastuzumab/Nebuliumab combined with conventional chemotherapy for 4 weeks/course and 3 continuous courses of treatment to evaluate the efficacy of targeted therapy. The abundance of intestinal flora was analyzed using 16S rDNA sequencing technologies. Quantitative real-time PCR（qRT-PCR）was used to detect AIM2 mRNA expression levels in PBMC, which were divided into a high expression group and a low expression group according to the median digit. Pearson correlation analysis was used to investigate the relationship between AIM2 expression and the relative abundance of intestinal flora, the efficacy of targeted therapy and clinical features. Results At the phylum level, the relative abundance of Bacteroidetes (0.70±0.15) and Proteobacteria (0.71±0.21 ) in the high expression group of AIM2 was significantly lower than that in the low expression group （0.81±0.17，0.80±0.16）, and the relative abundance of Firmicutes (0.73±0.12) was significantly higher than that in the low expression group（0.64±0.08），and the differences were statistically significant（t=3.108，2.210，4.061，all P ＜ 0.05）. At the genus level, the relative abundance of Bacteroides (0.13±0.02) in the high expression group of AIM2 was significantly lower than that in the low expression group（0.19±0.04）, and the relative abundance of Enterococcus (0.31±0.08 vs 0.12±0.05) and Escherichia coli (0.18±0.04 vs 0.10±0.02) was significantly higher than that in the low expression group （0.12±0.05，0.10±0.02），and the differences were statistically significant (t=8.472, 153.462, 11.722, all P<0.05). Pearson correlation showed that at phylum level, AIM2 expression was positively correlated with the relative abundance of Firmicutes (r=0.598, P<0.05), and negatively correlated with the relative abundance of Bacteroides and Proteobacteria (r=-0.641，-0.520, all P<0.05). At the genus level，AIM2 expression was positively correlated with the relative abundance of Enterococcus and Escherichia coli (r=0.529, 0.577, all P<0.05), and negatively correlated with the relative abundance of Bacteroides (r=-0.574, P<0.05). Among the 83 patients with advanced GC, 17 cases were effective and 66 cases were ineffective, and the Overall response rate (ORR) was 20.48%. The lesion diameter (5.73±0.74cm) and the proportion of cTNM stage IV (53.85%) in AIM2 high expression group were significantly lower than those in low expression group（6.08±0.51cm，75.00%）, and the targeted therapy ORR (30.77%) was higher than that in low expression group（11.36%）, with statistical significance (t/χ2/Z=2.477, 6.558, 4.780，all P < 0.05).Conclusion The expression of AIM2 in PBMC of advanced GC patients is closely related to the imbalance of intestinal flora and the effect of targeted therapy. Detection of AIM2 expression is conducive to guiding clinical screening of patients who benefit from targeted therapy.

参考文献/References:

[1] THRIFT A P, EL-SERAG H B. Burden of gastric cancer[J].Clinical Gastroenterology and Hepatology, 2020, 18(3): 534-542.
[2] LI Xuewei, XU Jun, XIE Jun, et al. Research progress in targeted therapy and immunotherapy for gastric cancer[J]. Chinese Medical Journal (England), 2022, 135(11): 1299-1313.
[3] FIDELLE M, RAUBER C, ALVES COSTA SILVA C, et al. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers[J].Science, 2023, 380(6649): eabo2296.
[4] TONG Yao, GAO Huiru, QI Qiuchen, et al. High fat diet, gut microbiome and gastrointestinal cancer[J].Theranostics, 2021, 11(12): 5889-5910.
[5] DING Chengsheng, YANG Xiao, LI Shuchun, et al. Exploring the role of pyroptosis in shaping the tumor microenvironment of colorectal cancer by bulk and single-cell RNA sequencing[J]. Cancer Cell International, 2023, 23(1): 95.
[6] SHARMA M, DE ALBA E. Structure, activation and regulation of NLRP3 and AIM2 inflammasomes[J]. International Journal of Molecular Sciences, 2021, 22(2): 872.
[7] SHARMA B R, KARKI R, KANNEGANTI T D. Role of AIM2 inflammasome in inflammatory diseases, cancer and infection[J]. European Journal of Immunology, 2019, 49(11): 1998-2011.
[8] ZHU Huan, ZHAO Ming, CHANG C, et al. The complex role of AIM2 in autoimmune diseases and cancers[J].Immunity Inflammation and Disease, 2021, 9(3): 649-665.
[9] 董建龙, 白松.AIM2 在结直肠癌发生发展中机制的研究进展[J]. 中国老年保健医学,2015(6):90-91,92. DONG Jianlong,BAI Song. Research advances in the mechanism of AIM2 in the development of colorectal cancer [J]. Chinese Journal of Geriatric Care, 2015(6): 90-91, 92.
[10] 郑鹏, 丰大利, 吴相柏. 肠道菌群移植在结直肠癌治疗中的应用进展[J]. 中国现代医生,2024,62(1):102-104. ZHENG Peng, FENG Dali, WU Xiangbai. Progress in the application of gut microbiota transplantation in the treatment of colorectal cancer [J]. China Modern Doctor, 2024, 62(1): 102-104.
[11] SHITARA K, FLEITAS T, KAWAKAMI H, et al. Pan-Asian adapted ESMO clinical practice guidelines for the diagnosis,treatment and follow-up of patients with gastric cancer[J]. ESMO Open, 2024, 9(2): 1022-1026.
[12] 蒋金玲, 周尘飞, 王超, 等.2022 年度胃癌研究和诊疗新进展[J]. 中国癌症杂志,2023,33(4):303-314. JIANG Jinling, ZHOU Chenfei, WANG Chao, et al. Advanced progress in research and diagnosis of gastric cancer in 2022[J]. China Oncology, 2023, 33(4): 303-314.
[13] GUAN Wenlong, HE Ye, XU Ruihua. Gastric cancer treatment: recent progress and future perspectives[J].Journal of Hematology & Oncology, 2023, 16(1): 57.
[14] 黄玉斌, 刘霄, 徐翠香, 等. 中晚期恶性肿瘤患者应用PD-1 抑制剂多周期治疗对外周血淋巴细胞亚群影响的动态变化研究[J]. 现代检验医学杂志,2022,37 (2):23-27. HUANG Yubin, LIU Xiao, XU Cuixiang, et al. Study on the dynamic changes of the effect of PD-1 inhibitor multicycle therapy on peripheral blood lymphocyte subsets in patients with advanced malignant tumors[J]. Journal of Modern Laboratory Medicine, 2022, 37(2): 23-27.
[15] WANG Haoying, LIU Mengxiao, ZENG Xi, et al. Cell death affecting the progression of gastric cancer[J]. Cell Death Discovery, 2022, 8(1): 377.
[16] QI Miao, DAI Dan, LIU Jin, et al. AIM2 promotes the development of non-small cell lung cancer by modulating mitochondrial dynamics[J]. Oncogene, 2020, 39(13): 2707-2723.
[17] FENG Xiaojia, SONG Zaozhi, HUANG Qihui, et al. AIM2 promotes gastric cancer cell proliferation via the MAPK signaling pathway [J]. Journal of Healthcare Engineering, 2022, 2022: 8756844.
[18] CHOU Weichun, GUO Zengli, GUO Hao, et al. AIM2 in regulatory T cells restrains autoimmune diseases[J].Nature, 2021, 591(7849): 300-305.
[19] MCCULLOCH J A, DAVAR D, RODRIGUES R R, et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1[J]. Nature Medicine, 2022, 28(3): 545-556.
[20] 饶贵安, 倪眺, 陈强, 等.MMP-2, AIM2 在直肠癌组织中的表达及其与新辅助放化疗疗效的关系[J]. 湖南师范大学学报(医学版),2021,18(2):199-202. RAO Guian, NI Tiao, CHEN Qiang, et al. Expression of MMP-2 and AIM2 in rectal cancer tissues and their relationship with the curative effect of neoadjuvant chemoradiotherapy[J]. Journal of Hunan Normal University(Medical Science), 2021, 18(2): 199-202.
[21] XIONG Siping, JIN Long, ZENG Chao, et al. An innovative pyroptosis-related long-noncoding-RNA signature predicts the prognosis of gastric cancer via affecting immune cell infiltration landscape [J].Pathology and Oncology Research, 2022, 28: 1610712.
[22] HUANG Kaida, LIN Yubiao, QIU Guoqin, et al. Comprehensive characterization of pyroptosis phenotypes with distinct tumor immune profiles in gastric cancer to aid immunotherapy[J]. Aging (Albany NY), 2023, 15(16): 8113-8136.
[23] WANG Qi, GAO Su, SHOU Yi, et al. AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis[J]. International Journal of Biological Sciences, 2023, 19(4): 1266-1283.

备注/Memo

备注/Memo:
基金项目：山西省基础研究计划青年科学研究项目，编号：202203021222351。
作者简介：李爱丽（1980-），女，本科，主治医师，研究方向：胃癌的诊疗，E-mail：58236900@qq.com。
更新日期/Last Update: 2025-03-15