Purpose. The aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated. Methods. Expression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database. Results. STMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation ( P < 0.05 ). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation. Conclusion. STMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.
BackgroundWhether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies.MethodsAll patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected.ResultsA total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation.ConclusionsFor ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status.
Background: The value of secondary cytoreductive surgery (SCS) for platinum-sensitive recurrent high grade serous ovarian cancer (HGSOC) patients and the effects of BRCA1/2 mutation status on the value of surgery are inconclusive.Methods: A retrospective analysis was conducted in HGSOC patients with primary platinum-sensitive recurrence who were admitted to the Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University and Shanghai General Hospital from January 2015 to August 2019. The DESKTOP Trial Score was used to assess whether patients could be included in the study. Relevant medical records were collected, including age at diagnosed, FIGO stage, germline BRCA1/2 mutations status, platinum-free interphase (PFI), recurrence characteristics, progression-free survival (PFS) and overall survival (OS).Results: A total of 195 HGSOC patients were included in the study, including 80 (41.0%) patients with BRCA1/2 germline mutation (BRCAmut) and 115 (59.0%) patients with germline BRCA1/2 wild-type (BRCAwt). SCS improved FPS in patients undergoing secondary cytoreductive surgery, regardless of BRCA1/2 mutation status (BRCAmut, median PFS, 16.3 vs 12.9 months, p = 0.003; BRCAwt, median PFS, 15.3 vs 11.0 months, p = 0.001). There was a significant survival benefit in BRCAwt patients undergoing SCS (median OS, 70.6 vs 52.5 months, p = 0.021), however, compared with chemotherapy alone, SCS in BRCAmut patients did not improve overall survival (median OS, 77.5 vs 76.8 months, p = 0.827).Conclusions: SCS is recommended for platinum-sensitive recurrent HGSOC patients with BRCAwt. BRCA1/2 genetic test for all HGSOC patients is necessary to specify appropriate post-recurrence treatment strategies.
Background Whether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies. Methods All patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1–3 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected. Results A total of 308 patients were enrolled in the study, including 108 patients with BRCA1/2 mutations (BRCAmut), and 200 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 36 BRCAmut patients (33.3%) and 59 BRCAwt patients (29.5%) received neoadjuvant chemotherapy. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 15.0 vs. 19.0 months, HR = 0.59; p = 0.03); however, there was no statistical difference in overall survival (OS) (median: 75.1 vs. 68.5 months, HR = 0.90; p = 0.72). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 14.6 months, HR = 1.02; p = 0.90) or OS (median: 54.0 vs. 56.4 months, HR = 1.23; p = 0.34). Multivariate analyses showed that the independent predictors of prolonged survival were PDS (p = 0.003), the absence of residual tumor after surgery (p = 0.010), and FIGO III stage (p = 0.011). Conclusions For advanced-stage ovarian cancer patients treated with NAC followed by IDS, PFS and OS were not significantly affected in BRCAwt patients. In BRCAmut patients, NAC-IDS resulted in a shortened PFS, but had no further effect on overall survival.
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