Gastroenterology

Gastroenterology

Volume 162, Issue 7, June 2022, Pages 1933-1947.e18
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer

https://doi.org/10.1053/j.gastro.2022.02.015Get rights and content

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 SaSc 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 SaSc: 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 SaSc: 64.0% vs 73.4%). Fecal signature SaSc 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 SaSc 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. (ClinicalTrials.gov, Number: NCT04638959).

Section snippets

Study Design and Cohort Participants

We conducted a large-scale, multicenter study. Patients with GCa and ChG were recruited in 3 cohorts (Supplementary Table 1). We collected gastric tissues and stool samples from both groups. After informed consent and completed questionnaires were acquired, a total of 1043 volunteers were recruited from 10 hospitals throughout China.

We established 3 independent cohorts. In the discovery cohort (N = 50) for the exploration of specific GCa-enriched bacteria, GCa tumor tissues, adjacent

Participant Cohorts and Quality Control

A total of 1043 subjects were included in this study. No significant statistical difference was observed in the baseline characteristics of subjects, such as age, sex, and body mass index (P > .05) (Supplementary Tables 1 and 2). A total of 5,326,219 sequences from 50 pairs of specimens (stool and tissue) were acquired from 16S rRNA sequencing, with 4494 operational taxonomic units found in mucosal samples and 1292 operational taxonomic units found in mucosal samples. According to the results

Discussion

The highest morbidity and mortality of GCa has been reported in East-Asian populations, particularly in China. A noninvasive, accurate, and simple screening strategy through fecal bacteria detection for high-risk populations and patients with early GCa is essential and highly desired. Hence, we carried out a large-scale, multicenter study and identified 2 promising fecal microbial signatures, Sa and Sc, for early screening and diagnosis of GCa, particularly the early stage of Gca. Sa and Sc, a

Acknowledgments

The authors thank all of the experts, professors, and coworkers for supporting this study: Dr Yao Zhang, Dr Qin-Yan Gao, Dr Xiao-Bo Li, Dr Hua Xiong, Dr Zhen-Hua Wang, Dr Wen-Yi Zhao, Dr Dong-Xing Cao, Dr Zi-Zhen Zhang, Dr Tian-Long Lin, Dr Chen Huang, Dr Xiang Xia, Dr An-Xiang Liu, and Dr Fu-Mei Yin for supporting specimen collection in Shanghai Renji Hospital; Dr Xiao-Yu Chen and Dr Yan-Shen Peng for providing pathological information of subjects; Qian Kang, Kai-Di Sun, Hang Liu, Yu-Yan Wang,

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    Data Availability Data, analytic methods, and study materials will not be made available to other researchers.

    Ethical Approval This study was approved by Ethics Committee of Shanghai Jiao-Tong University School of Medicine, Renji Hospital (Shanghai, China) (#2019-130).

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by National Key R&D Program of China (2020YFA0509200), National Natural Science Foundation of China (81830081, 81972203, 31970718, 82070570), Shanghai Municipal Health Commission, Collaborative Innovation Cluster Project (2019CXJQ02), Shanghai Sailing Program (21YF1425600), and Innovative research team of high-level local universities in Shanghai.

    Author names in bold designate shared co-first authorship.

    Author names in bold designate shared co-first authorship.

    Authors share co-first authorship.

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