Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of discordant lymphoma. Methods: The clinical data of one patient with discordant lymphoma at the PLA Strategic Support Force Characteristic Medical Center were retrospectively analyzed, and the related literatures were reviewed. Results: The patient was treated for thrombocytopenia and the examination showed splenomegaly. After hormone treatment, the platelet rebounded and thrombocytopenia occurred during hormone reduction. Splenectomy was performed. Postoperative pathological diagnosis of splenic marginal lymphoma was made and observed. Axillary lymph node enlargement occurred nine months later. Pathological diagnosis of diffuse large B-cell lymphoma was made by using lymph node biopsy, and the disease condition was alleviated after immunotherapy combined with chemotherapy. Conclusions Discordant lymphoma is rare and shows no special clinical manifestations. Its diagnosis should rely on pathological examination. Immunotherapy combined with chemotherapy may be more effective.