Background: Endometriosis (EM) is a chronic painful condition that predominantly affects women of reproductive age. Currently, surgery or medication can only provide limited symptom relief. This study used a comprehensive genetic analytical approach to explore potential drug targets for EM in the plasma proteome.Methods: In this study, 2,923 plasma proteins were selected as exposure and EM as outcome for two-sample Mendelian randomization (MR) analyses. The plasma proteomic data were derived from the UK Biobank Pharmaceutical Proteomics Project (UKB-PPP), while the EM dataset from the FinnGen consortium R10 release data. Several sensitivity analyses were performed, including summary-data-based MR (SMR) analyses, heterogeneity in dependent instruments (HEIDI) test, reverse MR analyses, steiger detection test, and bayesian co-localization analyses. Furthermore, proteome-wide association study (PWAS) and single-cell transcriptomic analyses were also conducted to validate the findings.Results: Six significant (p < 3.06 × 10^-5) plasma protein-EM pairs were identified by MR analyses. These included EPHB4 (OR = 1.40, 95% CI: 1.20 - 1.63), FSHB (OR = 3.91, 95% CI: 3.13 - 4.87), RSPO3 (OR = 1.60, 95% CI: 1.38 - 1.86), SEZ6L2 (OR = 1.44, 95% CI: 1.23 - 1.68) and WASHC3 (OR = 2.00, 95% CI: 1.54 - 2.59) were identified as risk factors, whereas KDR (OR = 0.80, 95% CI: 0.75 - 0.90) was found to be a protective factor. All six plasma proteins passed the SMR test (P < 8.33 × 10^-3), but only four plasma proteins passed the HEIDI heterogeneity test (PHEIDI > 0.05), namely FSHB, RSPO3, SEZ6L2 and EPHB4. These four proteins showed strong evidence of co-localization (PPH4 > 0.7). In particular, RSPO3 and EPHB4 were replicated in the validated PWAS. Single-cell analyses revealed high expression of SEZ6L2 and EPHB4 in stromal and epithelial cells within EM lesions, while RSPO3 exhibited elevated expression in stromal cells and fibroblasts.Conclusion: Our study identified FSHB, RSPO3, SEZ6L2, and EPHB4 as potential drug targets for EM and highlighted the critical role of stromal and epithelial cells in disease development. These findings provide new insights into the diagnosis and treatment of EM.

Background: Choriocarcinoma coexisting with endometrial carcinoma is rare. To the best of our knowledge, only one case of choriocarcinoma coexisting with endometrial carcinoma has been reported. Case presentation: Here, we present this case and provide a literature review. A 38-year-old unmarried nulliparous woman presented to the clinic with a menstrual disorder for more than 3 months. She then underwent a hysteroscopic procedure. The pathological findings were malignant, two types of carcinoma, and no transitional lesions were observed; about 85% of them were choriocarcinoma with smooth muscle infiltration and intravascular investigation of the thrombus; about 15% were highly differentiated endometrioid adenocarcinoma; Immunohistochemistry (endometrioid/choriocarcinoma): Vim (+ + / + + +), P40 (+ ±), CK5/6 multifocal ( ±), CK7 ( ±), EMA (+ ±), P16 multifocal ( ±), P53 (+ / + +), WT-1 (-/ + +), hCG (-/ + + +), CD138 (-/ + + +), Gly-3 (-/-), ER ( ±), PR (+ ±), Sall-4 (-/-), P21 (-/ +), P27 (-/ + + +), CyclinE (-/ + +), Ki67 positivity rate (10%/95%). We performed a laparoscopic hysterectomy, bilateral adnexectomy, and pelvic and para-abdominal lymph node dissection after five cycles of chemotherapy. She was diagnosed with choriocarcinoma with endometrial cancer, stage IVb choriocarcinoma and stage IA endometrial cancer. Postoperative radiochemotherapy was administered. The patient was disease-free 40 months after the treatment ended. Conclusion: We report a case of choriocarcinoma coexisting with endometrial carcinoma and provide a literature review that may help inspire additional studies in the future.