Pan-Cancer Integrative Analyses Reveal the Crosstalk Between the Intratumoral Microbiome, TP53 Mutation and Tumour Microenvironment

Abstract

Accumulating evidence suggests that the TP53 mutation, intratumoral microbiome, and tumour microenvironment (TME) are closely linked to tumourigenesis, yet the biological mechanisms underlying these connections remain unclear. To explore this, we collected multi-omics data—including genome, transcriptome, and tumour microbiome data—from a wide range of cancer types in The Cancer Genome Atlas (TCGA). Through a pan-cancer analysis, we identified significant correlations between intratumoral microbiota diversity and TP53 mutation status, particularly in hepatocellular carcinoma (HCC) and endometrial cancer (EC). Despite notable differences in microbiota composition between these two cancer types, we consistently observed that TP53 mutations were associated with reduced alpha-diversity. Additionally, we found that TP53 mutation status significantly influenced stromal components within the TME, such as a strong correlation between decreased endothelial cell abundance and TP53 mutation. Our integrated approach reveals the complex interplay between TP53 and factors regulating the host TME, offering new insights into cancer progression and potential therapeutic targets for future research.