The Synergetic Alterations Of Streptococcus Anginosus And Streptococcus Constellatus In Gastric Mucosa And Feces Of Gastric Cancer Patients

Objective This study aimed to explore alterations occurred in gastric mucosal and fecal microbiota in gastric cancer patients.We selected and validated two microbes as noninvasive,accurate,simple,sensitive and highly-accepted biomarkers that might assist to screen and diagnose gastric cancer,especially early gastric cancer patients.Methods We screen the synergetically differential species in paired gastric mucosal and fecal specimens between patients with 13 gastric cancer and 7 chronic gastritis by 16 S r RNA sequencing in cohort 1.We then measure their relative abundance by real-time quantitave PCR between gastric cancer group and gastritis group in cohort 2 to validate the sequencing results,which included 141 surgical tumor tissues and 217 stool specimens of gastric cancer patients,as well as 127 biopsy mucosas and 124 stools of gastritis patients.Among them,35 gastric cancer patients and 64 gastritis patients provided paired mucosas and feces.Through combination with tumor markers,we evaluated the efficacy of the targeted bacteria in the early warning,screening and diagnosis in gastric cancer.Results S.anginosus and S.constellatus were selected as differential bacteria of which relative abundance varied in gastric mucosa and feces of gastric cancer patients synergetically.q PCR also confirmed the sequencing results.Both of the mucosal and fecal relative abundance of S.anginosus and S.constellatus in gastric cancer patients increased significantly than gastritis patients(mucosal S.anginosus: P=0.013,S.constellatus: P=0.01;fecal S.anginosus: P<0.0001,S.constellatus: P<0.0001).The positive moderate correlation between the relative abundance of S.anginosus and S.constellatus existed between cancerous and paracancerous tissues.Also,the relative abundance of H.pylori and S.anginosus or S.constellatus demonstrate a positive correlation in cancerous tissues of gastric cancer patients.The tumor infiltration depth was the major factor influencing bacterial abundances.When the tumor did not infiltrate into the subserosal layer,the relative abundances of S.anginosus and S.constellatus in cancerous tissue were significantly higher than those of the gastric mucosa in gastritis group.The abundance elevation of both bacteria was more evident in early gastric cancer patients’ feces.Combining three tumor markers(CEA,CA19-9,CA72-4)with fecal abundance of S.anginosus and S.constellatus,the value of AUC was 0.88,which was much higher than that of tumor marker combination alone(P<0.0001).The AUC value of the combination of fecal bacterial abundance to distinguish early gastric cancer and gastritis patients was as high as 0.899 with the sensitivity of 80%.Conclusions The synergetic alterations between gastric mucosal tissues and feces microbiota occur in gastric cancer patients.Fecal biomarker based on S.anginosus and S.constellatus may help effectively screen early gastric cancer patients,help reduce the missed-diagnosis rate of ordinary endoscopy,as well as identify and evaluate patients with advanced gastric cancer.It is expected to become a noninvasive,accurate,simple,cost-effective and highly-accepted biomarker in gastric cancer screening.