Genetic alterations, including the overexpression of epidermal growth factor receptor (EGFR), play a crucial role in ovarian carcinogenesis. To date, EGFR targeting has shown limited antitumor effects in ovarian cancer when administered as monotherapy. We previously identified platelet-activating factor receptor (PAFR) as being overexpressed in ovarian cancer and found that its ligand PAF evoked EGFR phosphorylation. To determine whether PAFR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a PAFR antagonist (WEB2086) in conjunction with an EGFR inhibitor (AG1478).

Among the pro-inflammatory lipid mediators, platelet-activating factor (PAF) is a major primary and secondary messenger that binds to the PAF-receptor (PAFR). Epidermal growth factor (EGF) is a polypeptide growth factor that binds to the EGF-receptor (EGFR). Evidence suggests that both PAF and EGF play a significant role in oncogenic transformation, tumor growth, neoangiogenesis and metastasis, including ovarian cancer. PAF has the potential to transactivate EGFR in ovarian cancer cells. This study explores the mechanisms involved in EGF-induced PAF production.

Background/Objectives : Currently, no non-invasive detection method for endometrial cancer (EC) is recommended in clinical practice worldwide. This study aimed to evaluate the clinical value of detecting DNA methylation of CDO1 and CELF4 (CDO1m/CELF4m) in exfoliated cervical cells for the detection of EC in women with suspected endometrial lesions. Methods: A total of 2164 patients scheduled for hysteroscopic surgery due to suspected endometrial lesions at the Obstetrics and Gynecology Hospital of Fudan University between July 2023 and May 2024 were prospectively enrolled. Preoperative exfoliated cervical cells were collected for dual-gene methylation testing. Clinical data and endometrial thickness measured by transvaginal sonography (TVS) were recorded. Hysteroscopic histopathological diagnosis served as the gold standard to evaluate the performance of methylation testing alone and in combination with TVS. Results: This study included 2164 patients, comprising 33 EC cases, 31 cases of endometrial intraepithelial neoplasia (EIN), and 2100 cases of non-endometrial lesions, with mean ages of 51.7 ± 6.4, 49.5 ± 8.9, and 44.7 ± 9.8 years, respectively (p < 0.001). For EC detection, CDO1m/CELF4m positivity showed a sensitivity of 93.94% (95% CI: 79.77–99.26%), specificity of 96.7% (95% CI: 95.92–97.47%), positive predictive value (PPV) of 31.0% (95% CI: 25.96–36.53%), and negative predictive value (NPV) of 99.90% (95% CI: 99.63–99.98%). For EIN detection, the sensitivity was 83.87%, specificity 97.95%, PPV 37.68%, and NPV 99.76%. Combining TVS with DNA methylation detection further improved the sensitivity and NPV for both EC and EIN detection. Conclusions: DNA methylation detection in exfoliated cervical cells demonstrates high sensitivity and specificity for EC detection. The combination with TVS further enhances sensitivity and NPV, offering a simple and non-invasive triage strategy for patients with suspected endometrial lesions. This study was registered in China Clinical Trial Registry (ChiCTR2200055991) on 30 January 2023.