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

Gloria Ravegnini,Giulia Sammarini,Antonella Ioli,Giulio Rossi,Sabrina Angelini,Federica D’Amico,Viola Di Saverio,Federica Zanotti,Giorgia Valori,Monica Ricci,Patrizia Hrelia,Bruno Fosso,Silvia Turroni,Patrizia Brigidi

doi:10.3390/ijms21249735

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.

Highlights

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third cause of cancer-related death worldwide [1]
signet-ring cell carcinoma (SRCC) has distinct features compared to other GC, including adenocarcinomas (ADC)
Based on the mounting evidence and the need to disentangle GC heterogeneity, we investigated the possible alterations in microbiota composition and inferred functionality in order to identify potential biomarkers to better stratify the GC in SRCC and ADC

Summary

Introduction

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third cause of cancer-related death worldwide [1]. Due to its multifaceted and dynamic nature, the gut microbiome has been recently considered as a metabolically active organ, supporting several processes, including but not limited to energy metabolism, pathogen elimination and cancer development. Knowledge of the complex interactions between host and microbiota in cancer is still limited [20]. This is true for the gastric microbiota, which is largely understudied compared to the intestinal counterpart [21,22]. The majority of the studies evaluating stomach cancer have investigated the microbiome profile in mixed cohorts of GC patients without considering the different subtypes [23,24]. The knowledge on the potential differences in microbiota communities between SRCC and ADC GC is rather absent, leaving an open gap to fulfill

Methods

Results

Conclusion