CD47-a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features.

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

Combining photodynamic therapy and cascade chemotherapy for enhanced tumor cytotoxicity: the role of CTT2P@B nanoparticles.

The mitochondria act as the main producers of reactive oxygen species (ROS) within cells. Elevated levels of ROS can activate the mitochondrial apoptotic pathway, leading to cell apoptosis. In this study, we devised a molecular prodrug named CTT2P, demonstrating notable efficacy in facilitating mitochondrial apoptosis. To develop nanomedicine, we enveloped CTT2P within bovine serum albumin (BSA), resulting in the formulation known as CTT2P@B. The molecular prodrug CTT2P is achieved by covalently conjugating mitochondrial targeting triphenylphosphine (PPh3), photosensitizer TPPOH2, ROS-sensitive thioketal (TK), and chemotherapeutic drug camptothecin (CPT). The prodrug, which is chemically bonded, prevents the escape of drugs while they circulate throughout the body, guaranteeing the coordinated dispersion of both medications inside the organism. Additionally, the concurrent integration of targeted photodynamic therapy and cascade chemotherapy synergistically enhances the therapeutic efficacy of pharmaceutical agents. Experimental results indicated that the covalently attached prodrug significantly mitigated CPT cytotoxicity under dark conditions. In contrast, TPPOH2, CTT2, CTT2P, and CTT2P@B nanoparticles exhibited increasing tumor cell-killing effects and suppressed tumor growth when exposed to light at 660 nm with an intensity of 280 mW cm-2. Consequently, this laser-triggered, mitochondria-targeted, combined photodynamic therapy and chemotherapy nano drug delivery system, adept at efficiently promoting mitochondrial apoptosis, presents a promising and innovative approach to cancer treatment.

Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre.

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

Do ethnic chinese older adults with epithelial ovarian cancer survive a poorer prognosis?

BACKGROUND: The risk of suffering epithelial ovarian cancer (EOC) for women increases with age evidently, while the prognosis of older EOC patients remain unclear. Against the backdrop of the accelerate aging process in China, this paper investigates whether the older EOC patients have a lower overall survival probability than the younger patients based on the sample of ethnic Chinese population. METHODS: A total of 323 ethnic Chinese patients diagnosed as epithelial ovarian cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival probability between the younger group (< 70 years) and the older patients group (≥ 70 years). Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and independent prognostic factors were identified by univariate and multivariate Cox regression analyses. RESULTS: 43 patients were (13.3%) in the older patients group and 280 (86.7%) in the younger group. The distribution patterns between two groups were significantly different with regard to marital status, histologic type and FIGO stage. The median overall survival (OS) was significantly longer in the younger group than the older patients group (not reached vs. median 39 months, p < 0.05). The multivariate analysis demonstrated that the age (The older vs. the younger, HR: 1.967, P = 0.007), primary tumor laterality (HR: 1.849, P = 0.009), and FIGO stage (III vs. I, HR: 3.588, P = 0.001; and IV vs. I, HR: 4.382, P = 0.001; respectively) remained as important risk factors while Histology (HGSOC vs. CCOC, HR: 0.479, P = 0.025; and LGSOC/MOC/EC vs. CCOC, HR: 0.390, P = 0.034; respectively) and the number of lymph node dissected more than 10 was a protective factor (HR: 0.397, P = 0.008). In an analysis of 104 pairs of patients matched on the basis of the propensity score, the older patients group had significantly lower overall mortality (HR = 2.561, P = 0.002). CONCLUSION: Ethnic Chinese Older EOC patients have a worse prognosis than the younger patients.

Blocking CD47-SIRPα Signal Axis as Promising Immunotherapy in Ovarian Cancer.

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.

Novel prognostic nomograms to assess survival in high-grade serous ovarian carcinoma after surgery and chemotherapy: a retrospective cohort study from SEER database.

Background: Despite high-grade serous ovarian carcinoma (HGSOC) being the most common epithelial ovarian cancer, it is a heterogenous group of tumors with several histological subtypes. The goal of our study was to develop specifical models to predict the survival of actively treated, HGSOC. Methods: This retrospective cohort study included patients with HGSOC who had undergone surgery and chemotherapy between the years of 2010 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. A total of 3,788 cases were randomly divided into a training (n=2,591) and test set (n=1,197). Cox-LASSO algorithm and cross validation (based on lambda.1se) were used to identify survival factors in the training set. Nomograms were created and internally validated. We used Harrell's C-statistic to assess discrimination. The performance of each nomogram was evaluated using calibration plots. The clinical benefit of our models was evaluated using a decision curve analysis. Results: The significant prognostic factors were marital status, age, lymph node (LN) dissection, tumor size, residual disease, and the International Federation of Obstetrics and Gynecology (FIGO) stage, which were utilized to develop the nomogram for accurately predicting 3- and 5-year overall survival (OS). Among the above factors, except for marital status, the others were included in the model for cancer-specific survival (CSS). The C-indices for OS and CSS achieved 0.679 [95% confidence interval (CI): 0.660 to 0.699] and 0.678 (95% CI: 0.658 to 0.698), respectively, in the training set and 0.662 (95% CI: 0.633 to 0.690) and 0.680 (95% CI: 0.653 to 0.707), respectively, in the test set. The good consistency was illustrated using calibration plots. In comparison with models including only FIGO or the AJCC staging system, C-index in our study were increased by 4.5-7.0% for the development test and by 6.7-7.9% for the validation test. In addition, the nomograms had a bigger range of threshold probabilities in the decision curve analysis (DCA) curves. The high-risk subgroup had significantly less favorable survival than the low-risk subgroup. Conclusions: The present study indicated that the low-cost nomograms could be used as a potential prognostic tool specially for predicting survival in patients with HGSOC. Given the relatively small C-index, we still need to build a more accurate model to predict survival of HGSOC.

Radical surgery for pseudo-ovarian malignancy: a case report of bowel endometriosis with massive ascites.

Background: Endometriosis is a disturbing condition affecting about 10% of all reproductive aged women. The most severe form of endometriosis is deeply infiltrative endometriosis (DIE). Bowel is commonly affected in DIE. Treatment options of bowel endometriosis include surgery and medication, depending on many factors such as age, the severity of symptoms and desire for pregnancy. At present, the individualized comprehensive management of bowel endometriosis is still under exploration. Here we report an uncommon case of bowel endometriosis treated by radical surgery and postoperative high-dose progestin to enrich the clinical experience. Case Description: A 37-year-old woman was admitted to our hospital for suspected ovarian malignancy in the presence of pelvic mass, massive ascites and elevated CA-125. A laparoscopic radical surgery was performed, and she was diagnosed with bowel endometriosis. Considering the patient's high recurrence risk indicated by bowel endometriosis, massive ascites, severe adhesions, and dysmenorrhea, six-course gonadotropin-releasing hormone agonists therapy followed by high-dose progestin (two levonorgestrel intrauterine systems and subdermal implants) was administrated postoperatively to improve symptoms and prevent recurrence. No recurrence in bowels was observed by November 2021 (53 months). Conclusions: Both patient's desire and condition should be considered in the management of symptomatic bowel endometriosis. Optimal surgical removal is of great significance and individualized hormonal therapy may provide an additional component.

A rare case of highly differentiated follicular carcinoma in ovary with FGFR4 Gly388Arg polymorphism: a case report and literature review.

BACKGROUND: Highly differentiated follicular carcinoma (HDFCO) is a rare form of struma-derived thyroid-type carcinoma in ovary, defined as ovarian struma spreading beyond ovary but consisting of benign thyroid tissues. No more than 30 cases of HDFCO have been reported since it was first recognized in 2008. The clinicopathologic and molecular features of HDFCO remain unclear up till now. CASE PRESENTATION: A 38-year-old, para 1 gravida 5 woman has a long history of recurrent right ovarian cysts. Histological evaluation showed the tumor progressed from ovarian mature cystic teratoma (OMCT) to highly differentiated follicular carcinoma (HDFCO) during three relapses. Whole-exome sequencing revealed the germline FGFR4 Gly388Arg polymorphism. Repeated operations were performed to remove lesions for the first two relapses. On the third recurrence, the patient received radical surgery with subsequent thyroidectomy and radioactive iodine ablation. No evidence of disease was observed by February 2022 (8 months). CONCLUSIONS: The germline FGFR4 Gly388Arg polymorphism may accelerate the malignant transformation of HDFCO, probably by working as a second hit in the developing spectrum.

Neuroendocrine neoplasms of the ovary: an analysis of clinicopathological characteristics and prognosis with a focus on histological grading.

OBJECTIVE: Ovarian neuroendocrine neoplasm is a rare and highly heterogeneous neoplasm. This study is aimed to describe its demographic and clinicopathological features and identify its prognostic factors. METHODS: Clinical data of 399 patients diagnosed with ovarian neuroendocrine neoplasms between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were analysed retrospectively. Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and multivariate Cox regression analyses identified independent prognostic factors. RESULTS: The five-year survival rates of patients with different histological types (carcinoid tumour, neuroendocrine carcinoma and special type of carcinoid tumour) were 25.5%, 96.1% and 75.0%, respectively (P < 0.001). Multivariate Cox analysis revealed that in carcinoid tumours, advanced FIGO stage was the only predictor. Additionally, no significant difference was observed among stages II, III and IV using the log-rank test. In neuroendocrine carcinoma, an advanced FIGO stage and high-grade differentiation were risk factors, while chemotherapy was a protective factor. Among all ovarian neuroendocrine neoplasms with a known histological differentiation status, no significant difference was observed among different histological types; only high-grade differentiation was an independent risk factor, and chemotherapy was a protective factor. CONCLUSIONS: Patients with neuroendocrine carcinomas and carcinoid tumours of an advanced FIGO stage have a poor prognosis. Poor differentiation of neuroendocrine carcinomas indicates a short survival time, and adjuvant chemotherapy appears to be effective. Histological differentiation of ovarian neuroendocrine neoplasms is the most potent prognostic factor comparing to other known factors. Taken together, ovarian neuroendocrine neoplasms might be better classified as low- or high-grade ones rather than the currently used classification based on histological types in the future.

Tensor-Factorized Neural Networks.

The growing interests in multiway data analysis and deep learning have drawn tensor factorization (TF) and neural network (NN) as the crucial topics. Conventionally, the NN model is estimated from a set of one-way observations. Such a vectorized NN is not generalized for learning the representation from multiway observations. The classification performance using vectorized NN is constrained, because the temporal or spatial information in neighboring ways is disregarded. More parameters are required to learn the complicated data structure. This paper presents a new tensor-factorized NN (TFNN), which tightly integrates TF and NN for multiway feature extraction and classification under a unified discriminative objective. This TFNN is seen as a generalized NN, where the affine transformation in an NN is replaced by the multilinear and multiway factorization for tensor-based NN. The multiway information is preserved through layerwise factorization. Tucker decomposition and nonlinear activation are performed in each hidden layer. The tensor-factorized error backpropagation is developed to train TFNN with the limited parameter size and computation time. This TFNN can be further extended to realize the convolutional TFNN (CTFNN) by looking at small subtensors through the factorized convolution. Experiments on real-world classification tasks demonstrate that TFNN and CTFNN attain substantial improvement when compared with an NN and a convolutional NN, respectively.