Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer

• DOI: 10.1053/j.gastro.2022.02.015
• Publication Date: 2022-02-12T15:42:07Z
• Authors: Cheng-Bei Zhou; Si-Yuan Pan; Peng Jin; Jia-Wen Deng; Jin-Hui Xue; Xin-Yue Ma; Yuan-Hong Xie; Hui Cao; Qiang Liu; Wei-Fen Xie; Xiao-Ping Zou; Jian-Qiu Sheng; Bang-Mao Wang; Hong Wang; Jian-Lin Ren; Si-De Liu; Yun-Wei Sun; Xiang-Jun Meng; Gang Zhao; Jin-Xian Chen; Yun Cui; Pei-Qin Wang; Hui-Min Guo; Lang Yang; Xin Chen; Jia Ding; Xiao-Ning Yang; Xin-Ke Wang; Ai-Hua Qian; Li-Dan Hou; Zheng Wang; Ying-Xuan Chen; Jing-Yuan Fang
• Keywords: Feces; 0303 health sciences; 03 medical and health sciences; Stomach Neoplasms; Streptococcus anginosus; Humans; Streptococcus constellatus; Early Detection of Cancer; 3. Good health

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.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.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 Sa∪Sc 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 Sa∪Sc: 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 Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪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 Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort.Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).