Multiomics-based Analysis Reveals Differences in intratumoral microbiota and Prognostic in Gastric Cancer Patients with Different BMI

Abstract

Body mass index (BMI) is considered a significant prognostic factor for tumor outcomes;however, the role of BMI in gastric cancer (GC) remains controversial. Currently, there is a lack of research investigating the impact of BMI on GC from the perspective of intratumoral microbiota. This study aimed to compare and analyze the differences in and functions of intratumoral microbiota among GC patients with varying BMIs, aiming to ascertain whether specific microbial features are associated with prognosis in low-BMI gastric cancer patients.A retrospective analysis of the clinicopathological features and prognosis of 5567 patients with different BMIs were performed between January 2010 and December 2019. Tumor tissues from 189 GC patients were collected for 16S rRNA sequencing, 64 samples were selected for transcriptome sequencing, and 57 samples were selected for untargeted metabolomic analysis.Clinical cohort analysis revealed that GC patients with a low BMI(LBMI) presented poorer clinical and pathological characteristics than those with a nonlow- BMI༈NLBMI༉. LBMI has as a significant independent risk factor for adverse prognosis, potentially exerting immunosuppressive effects on postoperative adjuvant chemotherapy. 16S rRNA sequencing revealed no significant differences in the alpha and beta diversity of the intratumoral microbiota between the two groups of GC patients. However, LEfSe analysis revealed 32 differential intratumoral microbiota between the LBMI and NLBMI groups. Notably, g_Abiotrophia was significantly enriched in the LBMI group. In GC patients with LBMI, g_Abiotrophia was negatively correlated with the eosinophil, P2RY12, and SCN4B genes but positively correlated with LGR6. Metabolomic analysis further revealed a positive correlation between g_Abiotrophia and the purine metabolism products guanine and idp.LBMI is an independent risk factor for poor prognosis in patients with gastric cancer and may have inhibitory effects on postoperative adjuvant chemotherapy. There are differences in intratumoral microbiota between GC patients with different BMIs, along with distinct immune cell infiltration and metabolic characteristics.g_Abiotrophia may promote the occurrence and development of GC by regulating eosinophils and purine metabolism pathways, providing new solutions for precision treatment of GC.