Recently, the news of “a family of five infected with Helicobacter pylori” has sparked heated discussions. Helicobacter pylori is a highly contagious bacterium that can cause halitosis and gastritis after infection. Severe cases can induce gastric ulcers and even gastric cancer. At present, Helicobacter pylori has been positioned as a first-class carcinogen by the World Health Organization. The microbial environment of the gastrointestinal tract of the body is complex. In addition to Helicobacter pylori, there are thousands of bacteria. It is conceivable that some of these microorganisms may also cause gastric cancer like Helicobacter pylori. play an important role in the development process.
Two kinds of bacteria, accurate screening of gastric cancer
A study has compared the composition, diversity and richness of 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 Helicobacteraceae was significantly decreased in gastric cancer group, while the relative abundance of Streptococcus was significantly increased, and the diversity of intestinal microbes in gastric cancer group was also significantly increased [1], this difference may be exploited as gastric cancer Development of new means of diagnosis and treatment.
Recently, the team of Professor Fang Jingyuan, vice president and director of the Department of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, published a report in the authoritative medical journal “Gastroenterology” (Gastroenterology) published a paper [2], first reported the enrichment of two bacteria Streptococcus anginosus and Streptococcus constellatus in the feces of patients with precancerous lesions, early and advanced gastric cancer, It can be used as a non-invasive biomarker for early warning and screening of gastric cancer.
This is a large-scale, multi-center study that recruited 1,043 volunteers with gastric cancer or chronic gastritis from 10 hospitals in China, and collected gastric tissue and stool samples. They were divided into 3 independent cohorts, of which the discovery cohort (n=50) was used to explore specific gastric cancer-enriched colonies, including 25 gastric cancer patients and 25 chronic gastritis patients, all from Shanghai Renji Hospital; a 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 ; Validation cohort (n=483) from 9 hospitals in 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, was used to determine stool diagnosis in a multicenter setting Performance.
Figure 1 Study Design
Tumour tissue and feces were enriched in gastric cancer patients
16s rRNA gene analysis showed that compared with the chronic gastritis group, the proportions of Firmicutes and Streptococcus were significantly increased in the gastric cancer group. At the species level, Streptococcus angina ( Sa) and Streptococcus constellation (Sc) ratios were significantly increased in gastric cancer. This was also verified by qPCR. The relative abundance of Sa in tumor tissue was 1.9 times higher than that in control mucosa, and in stool, the relative abundance of Sa in gastric cancer group was higher than that in chronic gastritis group. 22.2 times, and the comparison for Sc also yielded similar results. The above findings suggest that Sa and Sc are significantly enriched in the tumor tissue and feces of gastric cancer patients compared with patients with chronic gastritis, and the enrichment degree is higher in feces.
Fig. 2 Increased abundance of Sa and Sc in feces and tumor tissue of gastric cancer
Next, the authors evaluated 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 in advanced gastric cancer, and compared with controls in the chronic gastritis group The mucosa was 7.5 times higher, in addition, the abundance of Sa and Sc in the stool of patients with early gastric cancer was also higher than that of patients with chronic gastritis, increased by 27.3 times and 10.9 times, respectively. From chronic gastritis to intraepithelial neoplasia (precancerous lesions of gastric cancer) and then to gastric cancer to undergo a multi-step and complex histological process, the researchers found that Sa and Sc were more abundant in the stool of patients with intraepithelial neoplasia. The number of patients with chronic gastritis increased significantly, that is, at the stage of precancerous lesions, these two bacteria were significantly enriched, suggesting that these two bacteria are important early warning signals for the occurrence of early gastric cancer.
The authors also evaluated the relationship between H. pylori and these two bacteria and found that Sa and Sc were slightly positively associated with H. pylori in gastric cancer tumor tissue, but in gastritis tissue There was no correlation and, moreover, the correlation was more pronounced in early gastric cancer than in advanced gastric cancer. The authors further divided patients with chronic gastritis into H. pylori-infected and uninfected H. pylori groups, and found that both bacteria were enriched in the gastric mucosa of the uninfected H. pylori gastritis group, but in stool, Sa There was no significant difference in the abundance of Sa and Sc in feces, meaning that gastric cancer screening using the abundance of Sa and Sc in stool was not affected by H. pylori infection.
High sensitivity, two cohorts validate diagnostic value
So, what is the value of Sa and Sc in the diagnosis of gastric cancer?
The authors first used a training cohort to evaluate the performance of fecal Sa and Sc in distinguishing healthy and early gastric cancer patients. At the best cut-off value, fecal Sa diagnosed The sensitivity of patients with early gastric cancer can reach 75.6% (that is, 75.6% of patients with early gastric cancer can be detected by this method), and the sensitivity of Sc can reach 84.4%, such asIf two bacterial species are considered at the same time (Sa ∪ Sc, that is, Sa-enriched or Sc-enriched or both are judged to have gastric cancer), the sensitivity can be increased 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 the screening sensitivity to 85.2%.
Finally, the authors used the validation cohort to validate the data obtained in the training cohort, and obtained consistent results in two independent cohorts, that is, compared with patients with chronic gastritis, Sa and Sc were highly enriched in the feces of gastric cancer patients, especially those with early gastric cancer, and these two bacteria indeed contributed 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 gastric cancer were misdiagnosed. Sa and Sc are also helpful in the diagnosis of advanced gastric cancer. When screening patients with advanced gastric cancer, Sa ∪ Sc can increase the sensitivity to 92.1%.
Combining the data of 993 patients in the training cohort and validation cohort, the sensitivity of Sa ∪ Sc for diagnosing early and advanced gastric cancer can reach 94.6% and 92.1%, respectively.
Gastric cancer is the fifth most common cancer in the world and the fourth most common cancer in the world[3]. Half of the gastric cancer deaths in the world are in China. It is very important to prevent gastric cancer and improve the prognosis of patients. At present, the early screening of gastric cancer is mainly through gastroscopy, which has disadvantages such as complicated operation and painful process. This study provides a non-invasive and highly sensitive candidate test for gastric cancer screening. The method has great clinical application value. If it can be promoted in clinical practice, it is believed that it can benefit more patients.
Author: Yin Qilei
Source: Cancer Frontline in Health
References
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.
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2. Zhou CB, Pan SY, 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.