This study indicated that bulk RNA sequencing, spatial transcriptome analysis, and small RNA sequencing of clinical samples from chemo-naive patients with HGSOC revealed that activated mesothelial cell-derived miR-135a-5p-enriched EVs in ascites affect cancer cells and activate the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, causing platinum resistance in cancer cells. Here, SOAT1 is linked to cancer.