Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer
Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer
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DOI：
10.1053/j.gastro.2022.02.015
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发表时间：
2022-05-13
期刊：
影响因子：
29.4
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Zhou, Cheng-Bei;Pan, Si-Yuan;Fang, Jing-Yuan
背景与目的：大多数胃癌（GCa）患者被诊断为晚期。我们的目的是研究新的粪便特征在GCa早期诊断中的临床应用。方法：这是一项观察性研究，包括来自中国10家医院的1043名患者。在发现队列中，对GCa和慢性胃炎（ChG）患者的配对样本（组织和粪便）进行16S核糖体RNA基因分析，以确定差异丰富的微生物。使用实时定量聚合酶链反应检测它们的相对丰度，以测试它们作为训练队列中的候选细菌。在验证队列中验证了它们的诊断功效。结果：上皮内瘤变、早期和晚期GCa患者肿瘤组织和粪便中血管链球菌（Sa）和星座链球菌（Sc）均显著富集（P < 0.05）。与晚期GCa相比，特征平行检测SaUSc或单一特征Sa/Sc在检测早期GCa方面表现出更高的灵敏度（Sa: 75.6% vs 72.1%, P < 0.05; Sc: 84.4% vs 64.0%, P < 0.001; SaUSc: 91.1% vs 81.4%, P < 0.01）（特异性：Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, SaUSc: 64.0% vs 73.4%）。粪便特征Sa U Sc鉴别晚期GCa优于Sa U CEA/Sc U CEA（敏感性：81.4%比74.2%、81.4%比72.3%,P < 0.01；特异性：73.4%比81.0%、73.4%比81.0%）。在验证队列中验证了SaUSc在早期和晚期GCa诊断中的表现。结论：粪便Sa和Sc是无创、准确、敏感的早期GCa预警信号。
BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test SaUSc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and SaUSc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and SaU Sc: 64.0% vs 73.4%). Fecal signature Sa U Sc outperformed Sa U CEA/Sc U CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of SaUSc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa.