Xiaolin Luo

MED12 Dictates Epithelial Ovarian Cancer Cell Ferroptosis Sensitivity via YAP–TEAD1 Signaling

Epithelial ovarian cancer (EOC) represents the most lethal malignancy arising from the female reproductive tract, largely due to the clinical challenge of chemotherapy resistance. Recent studies indicate that ferroptosis—a distinct form of programmed cell death driven by iron accumulation and lipid peroxidation, could potentially exploit a vulnerability in chemoresistant cancer cells. Here, we identify MED12 as a critical regulator of ferroptosis sensitivity in EOC through modulation of the YAP–TEAD1 signaling pathway. Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis inducers (RSL3 and Erastin), as evidenced by reduced IC50 values. Transcriptomic and chromatin accessibility analyses reveal that MED12 loss activates YAP signaling through TEAD1 upregulation, increasing chromatin accessibility at YAP–TEAD1 target loci and elevating the expression of downstream effectors CYR61 and CTGF. Pharmacological inhibition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP–TEAD1–ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic strategy in ovarian cancer.

The impact of lymph node dissection on survival in patients with clinical early-stage ovarian cancer

To estimate the impact of lymph node dissection on survival in patients with apparent early-stage epithelial ovarian cancer (EOC). We conducted a retrospective review of patients with clinical stage I-II EOC. All patients underwent primary surgery at Sun Yat-sen University Cancer Center between January 2003 and December 2015. Demographic features and clinicopathological information as well as perioperative adverse events were investigated, and survival analyses were performed. A total of 400 ovarian cancer patients were enrolled, and patients were divided into 2 groups: 81 patients did not undergo lymph node resection (group A), and 319 patients underwent lymph node dissection (group B). In group B, the median number of removed nodes per patient was 25 (21 pelvic and 4 para-aortic nodes). In groups A and B, respectively, the 5-year progression-free survival (PFS) rates were 83.3% and 82.1% (p=0.305), and the 5-year overall survival (OS) rates were 93.1% and 90.9% (p=0.645). The recurrence rate in the retroperitoneal lymph nodes was not associated with lymph node dissection (p=0.121). The median operating time was markedly longer in group B than in group A (220 minutes vs. 155 minutes, p<0.001), and group B had a significantly higher incidence of lymph cysts at discharge (32.9% vs. 0.0%, p<0.001). In patients with early-stage ovarian cancer, lymph node dissection was not associated with a gain in OS or PFS and was associated with an increased incidence of perioperative adverse events.