Zhang P, Xu J F, Zhou Y B
Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266003,China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2024 Jul 25;27(7):702-710. doi: 10.3760/cma.j.cn441530-20240109-00012.
To investigate the relationship between efficacy of neoadjuvant chemotherapy (NACT) for gastric cancer and gastric microecology. This was a retrospective observational study using fresh frozen operative specimens. The specimens had been stored in the tumor sample bank of the Department of Gastrointestinal Surgery of the Affiliated Hospital of Qingdao University from January 2017 to January 2023 after having been collected from 31 patients with pathologically diagnosed gastric cancer who had no metastases and had received only neoadjuvant chemotherapy preoperatively. The study patients had all successfully undergone radical gastric cancer surgery. Patients with metastases or other primary tumor foci and/or had received other therapies within 1 month prior to surgery, including immunotherapy, targeted therapies and probiotics, were excluded. The tumors were graded and grouped in accordance with the 8th edition of the American Joint Committee on Cancer staging system and the Tumor Regression Grading System (TRG) of the College of American Pathologists. Those with TRG Grades 0-1, ypT0-1 and ypN0 were classified as responsive (Group R, 12 cases), whereas those with TRG Grades 2-3 and ypT2-4 or ypN+ were classified as non-responsive (Group NR, 19 cases). The fresh frozen samples were processed and analyzed using 16S rRNA sequencing. Alpha and beta diversity analyses were performed using the Q2-diversity plug-in for QIIME2 and STAMP was used to determine the default parameters and differentially enriched bacterial taxa in the two groups. High-dimensional class comparisons were performed by effect size linear discriminant analysis, and potential functional distributions of microbiomes were predicted using PICRUST2 (v2.3.0-b) software. Groups R and NR did not differ significantly in sex, age, body mass index, smoking history, tumor location, cTNM stage before NACT, and neoadjuvant chemotherapy (all >0.05), whereas tumor size and ypTNM stage after NACT differed significantly between the two groups (both =0.001). Alpha and beta diversity analysis of the gastric microbiota did not reveal a statistically significant difference in alpha diversity between the two groups (>0.05), whereas there was a statistically significant difference in beta diversity between the two groups (=0.004). Four family-level bacterial taxa, namely , , , and , were enriched in the R group, whereas four bacterial taxa dominated by phylum Proteobacteria were enriched in the NR group. Metabolic pathways of various amino acids, including citric acid cycle and alanine, were found to be potentially predictive. There are significant differences in the abundance and composition of gastric microecology in gastric cancer patients with different responses to NACT.
探讨胃癌新辅助化疗（NACT）疗效与胃微生态之间的关系。这是一项使用新鲜冷冻手术标本的回顾性观察研究。标本于2017年1月至2023年1月期间，从31例经病理诊断为胃癌且无转移、术前仅接受新辅助化疗的患者中收集后，保存在青岛大学附属医院胃肠外科肿瘤样本库中。研究患者均成功接受了胃癌根治术。排除有转移或其他原发性肿瘤病灶和/或在手术前1个月内接受过其他治疗（包括免疫治疗、靶向治疗和益生菌）的患者。根据美国癌症联合委员会第8版分期系统和美国病理学家学会的肿瘤退缩分级系统（TRG）对肿瘤进行分级和分组。TRG分级为0 - 1、ypT0 - 1和ypN0的患者被归类为反应组（R组，12例），而TRG分级为2 - 3且ypT2 - 4或ypN +的患者被归类为无反应组（NR组，19例）。使用16S rRNA测序对新鲜冷冻样本进行处理和分析。使用QIIME2的Q2 - diversity插件进行α和β多样性分析，并使用STAMP确定默认参数以及两组中差异富集的细菌分类群。通过效应大小线性判别分析进行高维类别比较，并使用PICRUST2（v2.3.0 - b）软件预测微生物群的潜在功能分布。R组和NR组在性别、年龄、体重指数、吸烟史、肿瘤位置、NACT前的cTNM分期和新辅助化疗方面均无显著差异（均>0.05），而两组之间NACT后的肿瘤大小和ypTNM分期差异显著（均=0.001）。胃微生物群的α和β多样性分析显示，两组之间α多样性无统计学显著差异（>0.05），而两组之间β多样性有统计学显著差异（=0.004）。R组中富集了四个科级细菌分类群，即 、 、 和 ，而NR组中富集了以变形菌门为主的四个细菌分类群。发现包括柠檬酸循环和丙氨酸在内的各种氨基酸的代谢途径具有潜在预测性。对NACT反应不同的胃癌患者胃微生态的丰度和组成存在显著差异。
