Recently, "a family of five infected with Helicobacter pylori" news caused a hot discussion, Helicobacter pylori is a highly contagious bacterium, after human infection, light will lead to bad breath gastritis, heavy will induce gastric ulcers and even stomach cancer, at present, Helicobacter pylori has been positioned by the World Health Organization as a first-class carcinogen. In addition to Helicobacter pylori, there are thousands of bacteria in the body's gastrointestinal microbial environment, and it is conceivable that some of these microorganisms may play an important role in the development of gastric cancer like Helicobacter pylori.
Two kinds of bacteria, accurate screening for stomach cancer
Studies have compared the composition, diversity and richness of the gastric mucosal microbial communities in patients with chronic gastritis, intestinal metaplasia and gastric cancer, and found that compared with the gastritis group and the intestinal metaplasia group, the relative abundance of Helicobacteriaceae in the gastric cancer group decreased significantly, while the relative abundance of streptococcus was significantly increased, and the intestinal microbial diversity in the gastric cancer group also increased significantly[1], this difference may be used as a new means of gastric cancer diagnosis and treatment.
Recently, the team of Professor Fang Jingyuan, vice president of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine and director of the Department of Gastroenterology, published an article in the authoritative medical journal Gastroenterology[2], which first reported the enrichment of two bacteria in the feces of Streptococcus anginosus and Streptococcus constellatus in the feces of patients with precancerous lesions and early and advanced gastric cancer. Can be used as a non-invasive biomarker for early warning and screening for stomach cancer.
It was a large-scale, multicenter study in which a total of 1,043 volunteers with stomach cancer or chronic gastritis were recruited from 10 hospitals in China to collect samples of their stomach tissue and stool. It was divided into 3 separate cohorts, in which the discovery cohort (n=50) was used to explore specific gastric cancer-enriched colonies, including 25 patients with gastric cancer and 25 patients with chronic gastritis, all from Shanghai Renji Hospital; the training cohort (n=510) was used to test the reliability of candidate colonies on a larger scale, including 216 patients with chronic gastritis, 51 patients with early gastric cancer, and 243 patients with advanced gastric cancer, all from Shanghai Renji Hospital; the validation cohort (n=). 483) 9 hospitals from Beijing, Tianjin, Shanghai and other places, including 227 patients with chronic gastritis and 100 patients with early gastric cancer and 113 patients with advanced gastric cancer, were used to determine the diagnostic manifestations of feces at the multicenter scale.
Figure 1 Study design
Gastric cancer patients with tumor tissue and fecal bacteria enriched
16s rRNA gene analysis showed that compared with the chronic gastritis group, the proportion of phylum pachyderma and streptococcus spp. in the gastric cancer group was significantly increased, and at the species level, the proportion of Streptococcus pharyngeal angina (Sa) and Streptococcus constellation (Sc) increased significantly in gastric cancer. This was also verified by qPCR, where the relative abundance of Sa in tumor tissue was 1.9 times higher than that of the control mucosa, while in feces, the relative abundance of Sa in the gastric cancer group was 22.2 times higher than in the chronic gastritis group, and a similar result was obtained for sc. The above findings suggest that Sa and Sc are significantly enriched in tumor tissue and feces in patients with gastric cancer compared with patients with chronic gastritis, and more abundant in feces.
Fig. 2 Increased abundance of sa and sc in gastric cancer fecal and tumor tissue
The authors then assessed the effect of the depth of tumor invasion on Sa and Sc and found that the abundance of Sa in early gastric cancer tumor tissue was 2.6 times higher than that of advanced gastric cancer, 7.5 times higher than that of the control mucosa in the chronic gastritis group, and in addition, the abundance of Sa and Sc was also higher in the feces of patients with early gastric cancer than in patients with chronic gastritis, increasing by 27.3 times and 10.9 times, respectively. From chronic gastritis to intraepithelial neoplasia (precancerous lesions of gastric cancer) to gastric cancer to go through a multi-step, complex histological process, the researchers found that Sa and Sc in the feces of patients with intraepithelial neoplasia has been significantly higher than that of patients with chronic gastritis, that is, in the precancerous stage, these two bacteria have shown significant enrichment, suggesting that these two bacteria are important warning signs of early gastric cancer.
The authors also evaluated the relationship between Helicobacter pylori and the two bacteria, and found that Sa and Sc had a slight positive correlation with Helicobacter pylori in gastric cancer tumor tissue, but no correlation in gastritis tissue, and in addition, this correlation was more pronounced in early gastric cancer than in advanced gastric cancer. The authors further divided patients with chronic gastritis into the helicobacter pylori infection group and the uninfected Helicobacter pylori group, and found that both bacteria were enriched in the gastric mucosa of the uninfected Helicobacter pylori gastritis group, but in the feces, there was no significant difference in Sa and Sc abundance between the two groups, meaning that gastric cancer screening using the abundance of Sa and Sc in feces was not affected by Helicobacter pylori infection.
High sensitivity, two large queues verify diagnostic value
So, what is the value of Sa and Sc in stomach cancer diagnosis?
The authors first used a training cohort to evaluate the performance of Sa and Sc in the stool to distinguish healthy people from patients with early gastric cancer, and at optimal cut-off values, the sensitivity of Sa in the stool for diagnosing patients with early gastric cancer could reach 75.6% (i.e., 75.6% of patients with early gastric cancer could be detected by this method), while sc sensitivity could reach 84.4%, if two strains (Sa ∪ Sc, That is, Sa enrichment or Sc enrichment or both are judged to have stomach cancer), which can increase the sensitivity to 91.1%, and the false negative rate is only 8.9%. For patients with advanced gastric cancer, Sa∪Sc plus serum tumor marker carcinoembryonic antigen (CEA) can increase screening sensitivity to 85.2%.
Finally, the authors validated the data obtained in the training cohort using a validation cohort and obtained more consistent results in two separate cohorts, namely that Sa and Sc were highly enriched in the stool of patients with gastric cancer compared to patients with chronic gastritis, especially in patients with early gastric cancer, and these two bacteria did contribute to the prediction of early gastric cancer. In the validation cohort, the sensitivity of Sa ∪ Sc was as high as 97.6%, indicating that only 2.4% of patients with early-stage gastric cancer had misdiagnosed. Sa and Sc also help in the diagnosis of advanced gastric cancer, with Sa ∪ Sc being able to increase sensitivity to 92.1% when screening patients with advanced gastric cancer.
Combining the data of 993 patients in the training and validation cohorts, the sensitivity of Sa ∪ Sc to the diagnosis of early and advanced gastric cancer was 94.6% and 92.1%, respectively.
Gastric cancer is the world's world's 5th incidence, mortality rate of the 4th cancer [3], the world's half of the world's stomach cancer deaths in China, early screening is for the prevention of gastric cancer and improve the prognosis of patients is very important, the current early screening of gastric cancer is mainly through gastroscopy, there are complex operations, painful process and other shortcomings, and the study of this paper provides a non-invasive, high-sensitivity candidate examination method for gastric cancer screening, with great clinical application value, such as can be promoted in the clinic, I believe that more patients can benefit.
Author: Yin Qilei
Source: Frontline of Cancer in the Health Community
bibliography
1. Png CW, Lee WJJ, Chua SJ, Zhu F, Yeoh KG, Zhang Y. Mucosal microbiome associates with progression to gastric cancer. Theranostics 2022;12:48-58.
2. Zhou C-B, Pan S-Y, Jin P, et al. Fecal signatures of Streptococcus anginosus and Streptococcus constellatus for non-invasive screening and early warning of gastric cancer. Gastroenterology 2022.
3. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians 2021;71:209-49.