Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Abstract

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

“…• The results demonstrated significant differences in the microbial profile and composition between early gastric cancer and advanced gastric cancer Ravegnini et al 2020 • 10 adenocarcinoma and 10 signet-ring cell carcinoma and their paired non-tumor counterparts…”

“…A recent study gave insight into the microbial composition in different subtypes of GC. Fusobacteria, Bacteroidetes, Patescibacteria were enriched in signet-ring cell carcinoma, whereas Proteobacteria and Acidobacteria were enriched in adenocarcinoma (Ravegnini et al, 2020). Dysbiosis of the oral microbiome has been linked to inflammatory bowel disease, colorectal cancer, and pancreatic cancer (Nakatsu et al, 2015;Atarashi et al, 2017;Gaiser et al, 2019).…”

Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice

“…In a previous study, using a magnetically controlled sampling capsule endoscope (MSCE), a dramatic decrease in the abundance of Bacteroidetes , Patescibacteria , and Actinobacteria was detected in the antibiotic-induced diarrhea model [ 50 ]. In contrast, the microbiota composition in signet-ring cell carcinoma (SRCC) tumor samples was significantly enriched in the phyla Fusobacteria, Bacteroidetes , and Patescibacteria [ 51 ]. The phylum Patescibacteria was enriched throughout the luminal content in the small intestine when compared with that of the colon of preterm lambs [ 52 ].…”

Isomaltulose Exhibits Prebiotic Activity, and Modulates Gut Microbiota, the Production of Short Chain Fatty Acids, and Secondary Bile Acids in Rats

“…A previous study showed that Patescibacteria was significantly enriched in the group with alcoholic liver disease compared to the control, treatment, and positive groups [ 38 ]. Another research study also reported that the abundance of Patescibacteria was elevated in the signet-ring cell carcinoma patients [ 39 ].…”