The landscape of bacterial presence in tumor and adjacent normal tissue across 9 major cancer types using TCGA exome sequencing

Abstract

Identification of microbial composition directly from tumor tissue permits studying the relationship between microbial changes and cancer pathogenesis. We interrogated bacterial presence in tumor and adjacent normal tissue strictly in pairs utilizing human whole exome sequencing to generate microbial profiles. Profiles were generated for 813 cases from stomach, liver, colon, rectal, lung, head & neck, cervical and bladder TCGA cohorts. Core microbiota examination revealed twelve taxa to be common across the nine cancer types at all classification levels. Paired analyses demonstrated significant differences in bacterial shifts between tumor and adjacent normal tissue across stomach, colon, lung squamous cell, and head & neck cohorts, whereas little or no differences were evident in liver, rectal, lung adenocarcinoma, cervical and bladder cancer cohorts in adjusted models. Helicobacter pylori in stomach and Bacteroides vulgatus in colon were found to be significantly higher in adjacent normal compared to tumor tissue after false discovery rate correction. Computational results were validated with tissue from an independent population by species-specific qPCR showing similar patterns of co-occurrence among Fusobacterium nucleatum and Selenomonas sputigena in gastric samples. This study demonstrates the ability to identify bacteria differential composition derived from human tissue whole exome sequences. Taken together our results suggest the microbial profiles shift with advanced disease and that the microbial composition of the adjacent tissue can be indicative of cancer stage disease progression.

Keywords

• Microbial landscape
• Cancer microbiome
• TCGA
• Exome sequencing