Yangjun Wu

YY1-induced USP43 drives ferroptosis suppression by FASN stabilization and subsequent activation of SLC7A11 in ovarian cancer

Abstract The ubiquitin-specific protease (USP) family is a major member of the deubiquitinating enzyme family that plays important and diverse roles in multiple tumors. The roles and mechanisms of action of USP family members in ovarian cancer are not well understood. This study aimed to screen all the USP family members and explored the specific function of USP43 in ovarian cancer. The expression levels of USP family members in ovarian cancer were screened using bioinformatics analysis, and the specific function of USP43 was explored through in vitro and in vivo experiments. Functional assays, including cell viability, ferroptosis, and tumor xenograft models, were employed. In short, USP43 drives the ferroptosis suppression by activating the expression of SLC7A11 through FASN-HIF1α pathway. USP43 is an important prognostic factor for ovarian cancer, with its overexpression promoting ovarian cancer progression and its knockdown inhibiting it. Mechanistically, USP43, which is transcriptionally activated by YY1, stabilizes FASN through deubiquitination, and FASN activates SLC7A11 expression by stabilizing HIF1α. Furthermore, the combination of cisplatin and the SLC7A11 inhibitor HG106 significantly inhibits the growth of ovarian tumors. Thus, targeting the USP43-FASN-HIF1α-SLC7A11 axis can inhibit ferroptosis and promote platinum sensitivity in ovarian cancer.

Management for perioperative complications of diaphragmatic surgery in ovarian cancer at a Chinese tertiary cancer center

Diaphragm is the common site of metastasis in advanced ovarian cancer. Diaphragmatic surgery is necessary to achieve complete resection. Relative complications also pose challenges to perioperative management. This study aims to explore the influencing factors and management strategies for perioperative complications of diaphragm surgery. This study retrospectively included 396 patients who underwent diaphragmatic surgery for advanced ovarian cancer at Fudan University Shanghai Cancer Center from July 2015 to June 2022. Diaphragm surgical methods were classified, and perioperative complications were regarded according to Memorial Sloan Kettering Cancer Center criteria. Clinical characteristics and perioperative complications were analyzed to find correlations to establish the nomogram. Among the 396 patients, 163 patients (41.2%) suffered from perioperative complications. Pleural effusion (33.1%) and pneumothorax (5.3%) were the most commonly reported. Patients with longer surgery duration (>3 hours) (p=0.003) and who underwent diaphragmatic incision surgery (p=0.004) had a higher incidence of postoperative complications. The incidence of postoperative pleural effusion was significantly higher in patients who underwent diaphragm full-thickness resection (49.3%) than diaphragmatic stripping (29.5%) (p=0.001), and patients who underwent diaphragm full-thickness resection are more likely to require drainage (p=0.001). Multi-variate analyses showed that stage IV tumor, long operation time, and diaphragm full-thickness resection are associated with postoperative pleural effusion. Pleural effusion is the most common complication of diaphragmatic surgery in patients with ovarian cancer. Routine placement of prophylactic chest tubes is not appropriate for all patients undergoing diaphragmatic surgery. Our nomogram could help to predict its risk and indicate prophylactic management.