Humans ; Ovarian Neoplasms/drug therapy* ; Folate Receptor 1/metabolism* ; Female ; Immunohistochemistry/standards* ; Consensus ; Biomarkers, Tumor/metabolism* ; Fallopian Tube Neoplasms/pathology*

OBJECTIVES: Ovarian cancer is a common gynecologic malignancy, with poor prognosis in advanced stages. This study aimed to identify differentially expressed long noncoding RNA (lncRNA) associated with ovarian cancer prognosis and to explore the effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells. METHODS: Ovarian cancer-related lncRNA datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed and prognostically relevant tumor-suppressive lncRNAs were screened using lncRNA sequencing combined with clinical data. Reverse transcription PCR (RT-PCR) was used to detect the expression of lncRNA RP11-499E18.1 in ovarian cancer tissues, adjacent normal tissues, the IOSE80 normal ovarian epithelial cell line, and various ovarian cancer cell lines. Fluorescence in situ hybridization (FISH) was performed to determine its subcellular localization. Ovarian cancer cell lines CaOV3 and SKOV3 were divided into 3 groups: a negative control (NC) group, a knockdown (si-RP11-499E18.1) group, and a overexpression (pcDNA-RP11-499E18.1) group. Methyl thiazolyl tetrazolium (MTT) and Transwell assays were used to assess the effects of lncRNA RP11-499E18.1 on cell proliferation and migration. Western blotting was used to evaluate its effect on epithelial-mesenchymal transition (EMT)-related molecules. BALB/c nude mice were injected with CaOV3 cells transfected with pcDNA-RP11-499E18.1 (experimental group) or empty vector (control group), and tumor growth was monitored. Immunohistochemistry was used to assess the expression of Caspase 3 and Ki67 in tumor tissues. RESULTS: LncRNA sequencing identified RP11-499E18.1 as a differentially expressed and associated with prognosis. GEO data analysis showed that low RP11-499E18.1 expression was correlated with shorter overall and progression-free survival (both P<0.05). Its expression was significantly lower in ovarian cancer tissues and cell lines compared to normal controls (P<0.05 or P<0.001), and it was localized in both the nucleus and cytoplasm. In CaOV3 and SKOV3 cells, proliferation rates increased significantly in the si-RP11-499E18.1 group and decreased in the pcDNA-RP11-499E18.1 group (P<0.05 or P<0.001). Cell migration was enhanced in the si-RP11-499E18.1 group and suppressed in the pcDNA-RP11-499E18.1 group. Overexpression increased E-cadherin and decreased vimentin expression, while knockdown had the opposite effect. Tumor volume in the mouse model was significantly smaller in the experimental group (P<0.001), with increased Caspase 3 and decreased Ki67 expression in tumor tissues (both P<0.05). CONCLUSIONS LncRNA RP11-499E18.1 inhibits proliferation, migration, and EMT of ovarian cancer cells, and its low expression is associated with poor prognosis.
Female ; Humans ; RNA, Long Noncoding/physiology* ; Ovarian Neoplasms/pathology* ; Cell Line, Tumor ; Animals ; Mice ; Mice, Nude ; Cell Proliferation ; Prognosis ; Mice, Inbred BALB C ; Gene Expression Regulation, Neoplastic ; Cell Movement ; Epithelial-Mesenchymal Transition

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Objective To assess the value of the MRI-based ovarian-adnexal reporting and data system (O-RADS MRI) for the diagnosis of adnexal masses. Methods A total of 407 patients who underwent dynamic contrast enhancement (DCE)-MRI and pathological examination (gold standard) at the Department of Radiology,Central Hospital of Wuhan between May 2017 and December 2022 were enrolled in this study.Two radiologists performed the O-RADS MRI scoring of adnexal masses according to MRI features and calculated the malignancy rate of adnexal masses by O-RADS MRI score,enhancement type,and mass type.Moreover,receiver operating characteristic curves were established to further evaluate the diagnostic values of O-RADS MRI score,enhancement type,and mass type for adnexal masses. Results A total of 502 adnexal masses were identified in the 407 patients enrolled in this study,including 364 benign masses and 138 malignant masses (including junctional masses).Radiologist 1 reported the malignancy rates of 0,0,5.4%,80.0%,and 89.7% and radiologist 2 reported the malignancy rates of 0,0,5.8%,86.2%,and 83.0% for the adnexal masses with the O-RADS MRI scores of 1-5,respectively.With O-RADS MRI ≥4 indicating malignant masses,the sensitivity,specificity,accuracy,positive predictive value,negative predictive value,false negative rate,and false positive rate were 94.2%,93.6%,93.8%,84.9%,97.7%,2.3%,and 15.1% for radiologist 1 and 93.4%,93.6%,93.6%,85.4%,97.4%,3.6%,and 14.6% for radiologist 2,respectively.The malignancy rates of the adnexal masses presenting no enhancement,cystic wall enhancement,type Ⅰ curve,type Ⅱ curve,and type Ⅲ curve were 0,1.3%,5.7%,81.2%,and 89.0% as reported by radiologist 1 and 0,1.2%,11.3%,87.6%,and 80.0% as reported by radiologist 2,respectively.The malignancy rates of the adnexal masses that were cystic lesions,cystic segregated lesions,solid lesions,cystic solid lesions,and cystic solid segregated lesions were 0,7.1%,38.7%,79.1%,and 89.8% as reported by radiologist 1 and 0,8.1%,37.8%,72.4%,and 89.6% as reported by radiologist 2,respectively.With type Ⅱ and type Ⅲ curves as the criteria for malignancy,the sensitivity of radiologists 1 and 2 was lower for cystic segregated lesions,both at 50.0%.For the masses containing solid components,radiologists 1 and 2 demonstrated low specificity,which was 57.7% and 56.5%,respectively.False-positive masses contained solid components and were mostly fibroadenomas or adnexal leiomyomas,while false-negative masses were mostly junctional cystadenomas with no or few solid components. Conclusions The O-RADS MRI risk stratification has a high diagnostic value for adnexal masses.Further evaluation and refinement are needed to reduce the false-positive rate.
Humans ; Female ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Adnexal Diseases/diagnosis* ; Ovarian Neoplasms/diagnosis* ; Ovary/pathology* ; Sensitivity and Specificity ; Middle Aged ; Adult ; Adnexa Uteri/diagnostic imaging* ; Young Adult ; Data Systems ; Aged

Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.
Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Carcinoma, Small Cell/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/therapy* ; Prognosis

Female ; Humans ; Uterine Neoplasms/pathology* ; Carcinoma, Endometrioid/pathology* ; Endometrial Neoplasms/pathology* ; Ovarian Neoplasms/pathology*

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.
Humans ; Female ; Colorectal Neoplasms/pathology* ; Hyperthermia, Induced ; Peritoneal Neoplasms/secondary* ; Rectal Neoplasms/therapy* ; Ovarian Neoplasms/therapy* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China