Intratumoral Microbiota Correlates with AP-2 Expression: A Pan-Cancer Map with Cohort-Specific Prognostic and Molecular Footprints

The AP-2 family is a group of key regulators in cancer, yet their relationship with intratumoral microbes remains undefined. The present pan-cancer workflow leveraged TCGA transcriptomic data to correlate expression of AP-2 representatives with bacterial abundance on the genus and species level, followed by cohort-specific survival modeling, clinical profiling, differential expression, weighted co-expression analysis, and chromatin proximity tests with AP-2 enrichment. Significant correlations between microbiota and AP-2 were observed in 18 of 33 analyzed tumor types; <i>TFAP2E-AS1</i> was most recurrent among AP-2 members, and Halomonas was most recurrent among genera. Further species-level verification and prognostic importance nominated three promising pairs: <i>Paraburkholderia fungorum-TFAP2E</i> in adrenocortical carcinoma (ACC), <i>Actinomyces oris-TFAP2E</i> in diffuse large B-cell lymphoma (DLBC), and <i>Cutibacterium granulosum-TFAP2B</i> in stomach adenocarcinoma (STAD). An attempt to define a consensus expression signature driven by microbiota and AP-2, yet independent of the specific species or family member, revealed genes regulating various biological processes and pathways. ACC and DLBC shared a consensus expression program, whereas STAD diverged; chromatin analysis showed AP-2 motifs near microbe-responsive genes in ACC and DLBC but not STAD, supporting cohort-specific regulation. Collectively, AP-2 family members emerge as plausible mediators of tumor microbiota-host interplay, warranting further mechanistic and translational research.