Microorganisms play very important roles in
carcinogenesis,
tumor progression, and resistance upon treatment. Due to the challenge of accurately acquiring samples and quantifying low-biomass tissue microorganisms, most studies have focused on the effect of gut microorganisms on
cancer treatments, especially the efficacy of
immunotherapy. Although recent publications reveal the potential interactions between intratumor microorganisms and the immune microenvironment, whether and to what extent the intratumor microorganism could affect progression and treatment outcome remain controversial. This study is aiming to evaluate the associations among intratumor microorganisms, DNA methylation
cancer driver genes, immune response, and clinical outcomes from a pan-
cancer perspective, using 6,876 TCGA samples across 21
cancer types. We revealed that
tumor microorganism
dysbiosis is closely associated with the abnormal
tumor methylome and/or tumor microenvironment, which might serve to enhance the proliferation ability and fitness for the
therapy of
tumors. These findings shed the light on a better understanding of the interactions between
tumor cells and
carcinogens during and after
tumor formation, as well as microorganism-associated methylation alterations that could further serve as
biomarkers for clinical outcome assessment.