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

Area of Science:

• Oncology
• Microbiome Research
• Genomics

Background:

• The TP53 gene mutation, intratumoral microbiome, and tumor microenvironment (TME) are implicated in cancer development.
• The precise biological mechanisms connecting these factors are not fully understood.

Purpose of the Study:

• To investigate the correlations between TP53 mutation status, intratumoral microbiota diversity, and TME composition.
• To elucidate the biological mechanisms underlying these interconnections in a pan-cancer context.

Main Methods:

• Utilized multi-omics data (genome, transcriptome, microbiome) from The Cancer Genome Atlas (TCGA).
• Performed pan-cancer analysis to identify correlations between TP53 mutation status and microbiota diversity.
• Analyzed the influence of TP53 mutation on TME stromal components.

Main Results:

• Significant correlations found between intratumoral microbiota diversity and TP53 mutation status in hepatocellular carcinoma (HCC) and endometrial cancer (EC).
• TP53 mutations were consistently associated with reduced alpha-diversity in intratumoral microbiota.
• TP53 mutation status significantly impacted TME stromal components, notably correlating with decreased endothelial cell abundance.

Conclusions:

• TP53 mutations are linked to reduced microbial diversity and altered TME, particularly in HCC and EC.
• The study reveals a complex interplay between TP53, the host TME, and the intratumoral microbiome.
• Findings offer novel insights into cancer progression and potential therapeutic strategies targeting these interactions.