Abstract
Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy. Recent studies have discovered a pivotal role of the intratumoral microbiota in various cancers, yet it remains elusive in ACC. Here, we explored the intratumoral microbiome data derived from in silico identification, further validated in an in-house cohort by bacterial 16S rRNA fluorescence in situ hybridization and lipopolysaccharide staining. Unsupervised clustering determined two naturally distinct clusters of the intratumoral microbiome in ACC, which was associated with overall survival. The incorporation of microbial signatures enhanced the prognostic performance of the clinical stage in an immunity-dependent manner. Genetic and transcriptomic association analyses identified significant upregulation of the cell cycle and p53 signaling pathways associated with microbial signatures for worsened prognosis. Our study not only supports the presence of intratumoral bacteria but also implies a prognostic and biological role of intratumoral microbiota in ACC, which can advance a better understanding of the biology of ACC.