CircRAD23B promotes proliferation and carboplatin resistance in ovarian cancer cell lines and organoids.

BACKGROUND: Circular RNAs (circRNAs) are involved in the regulation of progression and drug resistance in ovarian cancer (OC). In the present study, we aimed to explore the role of circRAD23B, a newly identified circRNA, in the regulation of carboplatin-resistant OC. METHODS: CircRAD23B expression levels were measured using qRT-PCR. The biological roles of circRAD23B were analysed using CCK-8, colony formation, EDU, flow cytometry, and cell viability assays. RNA pull-down and luciferase assays were used to investigate the interactions of circRAD23B with mRNAs and miRNAs. RESULTS: CircRAD23B was significantly increased in carboplatin-resistant OC tissues. CircRAD23B promoted proliferation and reduced sensitivity to carboplatin in cell lines and patient-derived organoids (PDOs), consistent with in vivo findings. Mechanistically, circRAD23B acted as a molecular sponge, abrogating its inhibitory effect on Y-box binding protein 1 (YBX1) by adsorbing miR-1287-5p. Rescue experiments confirmed that the pro-proliferation and carboplatin resistance mediated by circRAD23B was partially reversed by the upregulation of miR-1287-5p. CONCLUSIONS: Our results demonstrated, for the first time, the role of the circRAD23B/miR-1287-5p/YBX1 axis in OC progression and carboplatin resistance in cell lines, PDOs, and animal models, providing a basis for the development of targeted therapies for patients with OC.

The Gustave Roussy immune score as a novel scoring system for predicting platinum resistance in advanced high-grade serous ovarian cancer.

OBJECTIVE: This study was designed to investigate the relationship between the Gustave-Roussy immune score (GRIm-score) and platinum resistance in patients with advanced high-grade serous ovarian cancer (HGSOC). METHODS: We conducted a retrospective study of patients diagnosed with advanced HGSOC between January 2017 and December 2020. A nomogram was developed to predict the risk of platinum resistance. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Bootstrap analysis was utilized for internal validation. Additionally, we analyzed the risk factors for platinum resistance in patients who received neoadjuvant chemotherapy (NACT). RESULTS: A total of 232 patients with advanced HGSOC were included, 52 (22.4 %) of whom experienced relapse with platinum resistance. Multivariate logistic regression analysis revealed that high GRIm-score (OR = 4.174, P < 0.001), NACT (OR = 2.706, P = 0.017), PLT > 260 (OR = 2.233, P = 0.037) and non-R0 (OR = 2.526, P = 0.012) were independent risk factors for platinum resistance. The area under the curve (AUC) of the model was 0.802 (95 % CI 0.736-0.868), and the internally validated AUC of 1000 bootstrap samples was 0.798 (95 % CI 0.725-0.862). In NACT-treated patients, univariate and multivariate logistic regression analyses revealed that a low KELIM score (OR = 10.405, P = 0.001) and PLT > 260 (OR = 4.611, P = 0.014) were independent risk factors for platinum resistance. CONCLUSION: The GRIm-score and PLT count are important prognostic factors in patients with HGSOC. For precision treatment, the status of partially platinum-sensitive patients should also be considered.

Derivation and validation of a nomogram based on clinical characteristics to diagnose endometriosis associated ovarian cancer preoperatively.

PURPOSE: The preoperative diagnosis of endometriosis associated ovarian cancer (EAOC) remains challenging for lack of effective diagnostic biomarker. We aimed to study clinical characteristics and develop a nomogram for diagnosing EAOC before surgery. METHODS: A total of 87 patients with EAOC and 348 patients with ovarian endometrioma (OEM) were enrolled in our study. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were utilized to select variables and construct the prediction model. The performance of the model was assessed using receiver operating characteristic (ROC) analyses and calibration plots, while decision curve analyses (DCAs) were conducted to assess clinical value. Bootstrap resampling was used to evaluated the stability of the model in the derivation set. RESULTS: The EAOC patients were older compared to the OEM patients (46.41 ± 9.62 vs. 36.49 ± 8.09 year, P < 0.001) and proportion of postmenopausal women was higher in EAOC group than in the OEM group (34.5 vs. 1.5%, P < 0.001). Our prediction model, which included age at diagnosis, tumor size, cancer antigen (CA) 19-9 and risk of ovarian malignancy algorithm (ROMA), demonstrated an area under the curve (AUC) of 0.858 (95% confidence interval (CI): 0.795-0.920) in the derivation set (N = 304) and an AUC of 0.870 (95% CI: 0.779-0.961) in the validation set (N = 131). The model fitted both the derivation (Hosmer-Lemeshow test (HL) chi-square = 12.600, P = 0.247) and the validation (HL chi-square = 8.210, P = 0.608) sets well. CONCLUSION: Compared to patients with OEM, those with EAOC exhibited distinct clinical characteristics. Our four-variable prediction model demonstrated excellent performance in both the derivation and validation sets, suggesting its potential to assist with preoperative diagnosis of EAOC.

Visceral obesity determined by CT as a predictor of short-term postoperative complications in patients with ovarian cancer.

OBJECTIVE: To explore the association between visceral obesity and short-term postoperative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery. METHODS: The medical records of patients with advanced epithelial ovarian cancer were reviewed. The visceral fat area, subcutaneous fat area and total fat area at the L3/4 level were measured on a preoperative single-slice CT scan. The receiver operating characteristic (ROC) curve was used to calculate the optimal cutoff value for the visceral fat area. The relationship between the visceral fat area and the characteristics of ovarian cancer patients were analyzed. Univariable and multivariable logistic regression analyses were performed to investigate relationship between perioperative characteristics and short-term complications. RESULTS: According to the ROC curve, the best cutoff value of the VFA was 93 cm2. Of the 130 patients, 53.8% (70/130) had visceral obesity. Patients with visceral obesity were older than those with nonvisceral obesity (58.4 years old vs. 52.1 years old, p < 0.001). The proportion of patients with hypertension was higher (35.7 vs. 13.3%, p = 0.003). The total fat area and subcutaneous fat area were larger in patients with visceral obesity (294.3 ± 75.5 vs. 176.2 ± 68.7, p < 0.001; 158.9 ± 54.7 vs. 121.7 ± 52.6, p < 0.001). Compared with patients in the nonvisceral obese group, patients in the visceral obese group were more likely to have postoperative fever (21/70 30.0% vs. 8/60 1.25%, p = 0.023), leading to a longer length of hospital stay (21 days vs. 17 days, p = 0.009). The time from surgery to adjuvant chemotherapy for patients with visceral obesity was shorter (24 days vs. 19 days, p = 0.037). Multivariate analysis showed that visceral obesity (OR = 6.451, p < 0.001) and operation time (OR = 1.006, p < 0.001) were independent predictors of postoperative complications. CONCLUSION: Visceral obesity is an important risk factor for short-term postoperative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery.

Sister Mary Joseph nodule as cutaneous manifestations of metastatic ovarian cancer: A case report and review of the literature.

RATIONALE: The Sister Mary Joseph's nodule is an umbilical nodule resulting from the metastasis of malignant tumors in the pelvic and/or abdominal cavity. Sister Mary Joseph's nodules are very rare, and the morphology of the skin lesions is not specific and is easily misdiagnosed. Here, we report a case of cutaneous manifestations of metastatic ovarian cancer. PATIENT CONCERNS: The patient was admitted to our hospital because of abdominal distention, and a nodule was found in the umbilicus. A computerized tomography scan of the entire abdomen showed nodular soft tissue in the subcutaneous fat space of the umbilical area and multiple pelvic masses, which were suspected metastases of peritoneal and omentum ovarian cancer. INTERVENTIONS: To confirm the pathological diagnosis, posterior fornix puncture was performed. Pathological biopsy showed adenocarcinoma. Histological examination revealed a mass arising from high-grade serous carcinoma of the ovary. The patient received 2 cycles of chemotherapy with paclitaxel liposomes and carboplatin and underwent interval debulking surgery. Postoperative pathology was consistent with high-grade serous carcinoma of the ovary. Cancer involvement was observed in umbilical lesions. After the operation, the patient was given 6 cycles of chemotherapy with paclitaxel liposomes and carboplatin. OUTCOMES: The patient underwent follow-up until October 2020. A computerized tomography scan of the entire abdomen showed that the lymph nodes in the abdominal cavity were larger than before, suggesting a platinum-sensitive relapse. After receiving the same regimen of chemotherapy, carbohydrate antigen 125 dropped to the normal range, and consolidated treatment was administered for 3 cycles. Owing to her BRCA1 mutations, olaparib was administered for maintenance treatment. Until now, she had been in the outpatient clinic for regular follow-up visits. LESSONS: The umbilicus remains an infrequently examined area, which cannot be underestimated and warrants careful clinical follow-up and histological evaluation, as appropriate.

Ovarian high-grade serous carcinoma with elevated ß-human chorionic gonadotropin: A case report.

RATIONALE: Human chorionic gonadotropin (hCG) is a glycoprotein hormone secreted by the syncytiotrophoblasts of the placenta. However, hCG (particularly ß-hCG) is also expressed in many normal nontrophoblastic tissues. Here, we report the case of a 50-year-old woman diagnosed with ovarian high-grade serous carcinoma with elevated ß-hCG, which was insensitive to chemotherapeutic drugs and had a poor prognosis. PATIENT CONCERNS: A 50-year-old woman with abdominal distention was admitted to our hospital. Pelvic computed tomography and magnetic resonance imaging were highly suggestive of multiple metastases of ovarian cancer. Surprisingly, an elevation in ß-hCG levels was also measured. DIAGNOSIS AND INTERVENTIONS: The patient underwent laparoscopic examination and was diagnosed with high-grade serous ovarian carcinoma. After 2 prior chemotherapies with paclitaxel and carboplatin, the patient underwent cytoreductive surgery and continued receiving chemotherapy. However, recurrent lesions were observed during the period of chemotherapy, and the level of ß-hCG increased. Alternative chemotherapy with liposomal doxorubicin was administered, but it also had a poor therapeutic effect. OUTCOMES: The progression was rapid with a continuous increase in ß-hCG levels, and the patient died 9 months after surgery. LESSONS: Gynecologists should be aware of women with ovarian carcinoma with an elevated ß-hCG level, which suggests a poor prognosis.

Using mRNAsi to identify prognostic-related genes in endometrial carcinoma based on WGCNA.

AIMS: Cancer Stem Cells (CSCs) refers to heterogeneous tumor cells retaining the abilities of self-renewal and differentiation. This study used mRNAsi, which is an index to describe the similarity between tumor cells and CSCs, to define genes involved in endometrial carcinoma. MATERIALS AND METHODS: The mRNA expression profiles of 552 tumor samples and 23 non-tumor samples were calculated for differentially expressed genes. WGCNA was utilized to construct gene co-expression networks and classify screened genes into different modules. Univariate and multivariate Cox regression models were performed to identify and construct the prognostic model. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve, multivariate Cox regression analysis, and nomogram were used to assess the prognostic capacity of the six-gene signature. The screened genes were further validated by GEO (GSE17025) and qRT-PCR in EC tissues. KEY FINDINGS: 2573 upregulated and 1890 downregulated genes were identified. A total of 35 genes in the turquoise module were identified as key genes. With multivariate analysis, six genes (DEPDC1, FAM83D, NCAPH, SPC25, TPX2, and TTK) up-regulated in endometrial carcinoma were identified, and their higher expression was associated with a higher stage/age/grade. Moreover, ROC and Kaplan-Meier plots indicated these genes had a high prognostic value for EC. A nomogram was constructed for clinical use. In addition, we explored the pathogenesis involving six genes. The results showed that these genes may become pathogenic as their copy numbers changes and methylation level reduces. Finally, GSEA revealed these genes had a close association with cell cycle, etc. SIGNIFICANCE: These findings may provide new insights into the treatment of diseases.