An activation of interleukin-17C signaling drives cancerogenesis of endometriosis
Endometriosis -associated ovarian carcinoma (EAOC) is mostly malignant transformation from endometriomas.  However, the endometriosis cancerogenesis remains to be established.  Using spatial transcriptomic of human specimens of normal, endometriomas and EAOC, activation of Interleukin-17C (IL-17C) signaling is identified, with higher IL-17 receptor E (IL-17RE) expression in endometriotic cells, to be associated with cancerogenesis and which has no previous association with EAOC.  Elevated IL-17C concentration is found in peritoneal fluid in women with ovarian cancer and IL-17RE-overexpressed endometriosis mice.  In particular, IL-17C knockout reduces peritoneal fluid IL-17C concentration and inhibits ectopic lesion growth in endometriosis mice.  Besides, the role of IL-17C in the endometriosis cancerogenesis was investigated by blocking the IL-17C/IL-17RE, modulating IL-17RE and neutralizing IL-17C in endometriotic cells, endometrial organoids and endometriosis mice.  These data defined peritoneal fluid-mediated endometriosis cancerogenesis through IL-17C regulation and suggests that IL-17C/IL-17RE can thus potentially serve as novel targets for with high IL-17C. Overall design: Normal endometrium, endometriosis, and endometriosis associated ovarian cancer were analyzed by spatial transcriptomics