SOX9: Advances in Gynecological Malignancies

Transcription factors of the SOX family were first discovered in mammals in 1990. The sex-determining region Y box 9 belongs to the SOX transcription factor family. It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. Gynecological malignancies are tumors that occur in the female reproductive system and seriously threaten the lives of patients. Common gynecological malignancies include ovarian cancer, cervical cancer, and endometrial cancer. So far, the molecular mechanisms related to the incidence and development of gynecological malignancies remain unclear. This makes it particularly important to discover their common causative molecule and thus provide an effective therapeutic target. In recent years, studies have found that multiple mechanisms are involved in regulating the expression of the sex-determining region Y box 9, leading to the occurrence and development of gynecological malignancies. In this review, we discuss the prognostic value of SOX9 expression and the potential of targeting SOX9 for gynecological malignancy treatment. We also discuss progress regarding the role of SOX9 in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance.

Risk Factors For Perioperative Venous Thromboembolism in Patients With Gynecological Malignancies

Introduction：Venous thromboembolism (VTE), is a frequent postoperative complication of gynecologic malignancies during perioperative period.Although a number of risk factors for perioperative VTE with gynecological malignancies have been reported, the findings are diverse or even contradictory .In addition, most of the existing studies were retrospective case-control studies with small sample sizes .This study was a prospectively matched case-control study and aimed to specifically explore the risk factors related to surgery for perioperativeVTE in gynecologic malignancies.Material and methods：Overall,734 patients with gynecologic malignancies were enrolled in this study.54 patients who developed VTE were included as the case group. A total of 270 non-VTE patients matched in a ratio of 1:5 as a control group with the matched principle of the same ethnicity and similar date of surgery (difference ± 3 days). The demographic characteristics, clinical data, laboratory tests, surgical data, and data related to the occurrence of VTE were collected during the follow-up period. Conditional logistic regression models were used for univariate and multifactorial analyses. Factors related to surgical treatment, especially those could be intervened and prevented, were used as target factors, which were gradually corrected by demographic data, clinical data, laboratory tests and other factors related to surgery, and sensitivity analysis was performed.Results:The results of univariate analysis showed that age, place of residence, occupation, high-fat diet, menopause, comorbid chronic diseases, duration of upper extremity indwelling needle retention, disease diagnosis, sleep during hospitalization, admission albumin, surgical approach , duration of intensive care unit(ICU)admission, start of anticoagulant use, time to resume postoperative anal evacuation, duration of bed rest, duration of drinking abstinence, difference between postoperative and admission Caprini scores,duration of abdominal drainage tube retention, and intraoperative bleeding were risk factors for VTE in patients with perioperative gynecologic malignancies (P<0.05). Stepwise corrected multifactorial conditional logistic regression analysis showed that admission albumin<46.40 g/L and large difference between postoperative and admission Caprini scores were risk factors for the development of VTE in patients with gynecologic malignancies in the perioperative period, and the risk of VTE in patients with admission serum albumin<46.40 g/L was 4.885 times higher than that in patients with admission serum albumin≥46.40 g/L; The larger difference between postoperative and admission Caprini scores, the higher the risk of VTE, and a 1-point increase in the difference between postoperative and admission Caprini scores was associated with a 2.174-fold increase in the risk of VTE (95% CI: 1.255 to 3.766, P= 0.006).Conclusions: The main risk factors for perioperative VTE in gynecologic malignancies are serum albumin lower than 46.40 g/L and large difference between postoperative and admission Caprini scores. More attention should be paid to the dynamic changes of serum albumin and Caprini scores of patients in the perioperative period and those factors should be targeted to intervene in order to reduce the perioperative VTE.

Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial

BackgroundPatients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has demonstrated significant clinical efficacy across a range of common malignancies, justifying evaluation of this combination in rare gynecological cancers.MethodsThis multicenter phase II study enrolled 43 patients with advanced rare gynecological cancers. Patients received induction treatment with nivolumab and ipilimumab at a dose of 3 mg/kg and 1 mg/kg, respectively, every 3 weeks for four doses. Treatment was continued with nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or a maximum of 2 years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease (SD) by Response Evaluation Criteria In Solid Tumor V.1.1). Exploratory evaluations correlated clinical outcomes with tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB).ResultsThe objective response rate in the radiologically evaluable population was 36% (12/33 patients) and in the intention-to-treat population was 28% (12/43 patients), with additional 7 patients obtaining SD leading to a disease control rate of 58% and 44%, respectively. Durable responses were seen across a range of tumor histologies. Thirty-one (72%) patients experienced an immune-related adverse event (irAE) with a grade 3/4 irAE observed in seven (16%) patients. Response rate was higher among those patients with baseline PD-L1 expression (≥1% on tumor cells) but was independent of TMB.ConclusionsIpilimumab and nivolumab combination treatment has significant clinical activity with a favorable safety profile across a range of advanced rare gynecological malignancies and warrants further investigation in these tumor types.