Subtypes Of Ovarian Cancer Research Articles

Abstract C023: Variations in clinical presentation and outcomes of rare ovarian cancers by race and nativity

Abstract Introduction: Disparities in the prevalence of disease, medical access, and survival rates have been well documented in women with epithelial ovarian cancer. Black women tend to develop more aggressive tumors and have worse overall survival. Aside from race, however, nativity (region of birth) has been associated with variations in treatment outcomes. There is a paucity of research specifically about rare ovarian cancer subtypes, including germ cell (GC) and stromal cell (SC) tumors. Our study aims to provide a comparative analysis of clinical presentation and outcomes among women of Caribbean and US origin with GC and SC tumors, stratified by race. Methods: Analyses were conducted using the Florida Cancer Data Service (FCDS), the statewide cancer registry. Women who were diagnosed with GC and SC ovarian cancer subtypes from 1987 to 2017 were identified, and categorized as either US-born (USB) White, USB Black, Caribbean-born (CB)White, or CB Black. Abstracted data included patient-level demographic data, treatment histories, and all-cause overall survival. Statistical analyses were performed using chi-square, ANOVA, log-rank test, and Kaplan-Meier method, with the threshold for statistical significance set at p < 0.05. Results: 691 women with GC and SC were identified. There was a significant difference in mean age at diagnosis by race and nativity. USB Black women were diagnosed at the youngest mean age (34.4 yr, SD 20.62), followed by USB White (38.6 yr, SD 20.97), CB Black (43.9 yr, SD 20.79), and CB White (45.9 yr, SD 18.66)(p=0.002). CB White patients had the highest utilization of Medicaid (23.5%), while CB Black had the highest proportion of uninsured patients (22.2%)(p<0.001). There were no differences in stage, tumor characteristics (grade, histology, lymph vascular invasion) or treatments (surgery, chemotherapy, radiation) administered among the groups. CB Black women had a much lower prevalence of smoking (2.8%) compared to the other subgroups (CB White 23.5%5; USB White 28.1%; USB Black 16.9%, p=0.003). There were no significant differences in median OS by race and nativity (USB White 184 months; USB Black USB 244 months; CB White 270 months; CB Black CB 204 months; log-rank p=0.8). Conclusion: Despite a younger age of diagnosis in USB versus CB women, and Black women vs White women, there were no differences in survival outcomes in women with GC and SC ovarian cancers, even when considering variations in insurance coverage and smoking histories. While the long survival is likely due to the natural history of these tumors, the variation in age at diagnosis suggests variable susceptibility to tumor initiation by race and place of birth. Citation Format: Maurice J. Chery, Alex P. Sanchez-Covarrubias, Sophia H.L. George, Matthew P. Schlumbrecht. Variations in clinical presentation and outcomes of rare ovarian cancers by race and nativity [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C023.

Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma.

As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment. A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed. Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1-positive samples were more common in the chemoresistant group than in the platinum-sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis. This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.

Abstract B060: Dual blockade of BRD4 and the ATR/WEE1 pathway exploits ARID1A loss in clear cell ovarian cancer

Abstract Clear Cell Ovarian Cancer (CCOC) is one of the most challenging subtypes of ovarian cancer to treat as advanced stages are often chemo-resistant compared to the more common high-grade serous ovarian cancer (HGSOC). Limited treatment options are available for this devastating disease. Understanding the resistance mechanism and identifying effective therapeutic options for CCOC are clearly needed. Exploiting genetic alterations common in CCOC, such as ARID1A, is a rational strategy for combination therapies. ARID1A, an epigenetic tumor suppressor, is the most common genetic mutation in CCOC, with about 50% of CCOC demonstrating loss of ARID1A. ARID1A regulates the transcription of specific genes (e.g. c-myc) by altering the chromatin structure. We hypothesize that ARID1A loss increases CCOC cell dependency on chromatin remodeling and DNA repair pathways for survival. Through a drug screen, BET inhibitors and DNA damage response inhibitors were the most active monotherapies in ARID1A mutant CCOC. However, monotherapy efficacy needs to be further improved. We demonstrate in our study that the combination of BRD4 inhibitor (BRD4i) with DNA damage response (DDR) inhibitors (ATR or WEE1 inhibitors; e.g. BRD4i-ATRi) were synergistic at low doses leading to decreased survival, and colony formation in an ARID1A dependent manner. Combination BRD4i-ATRi caused significant tumor regression and increased overall survival in ARID1AMUT not ARID1AWT patient-derived xenograft (PDX) models. Combination BRD4i-ATRi significantly increased gH2AX, and decreased RAD51 foci and BRCA1 expression suggesting loss in the ability to repair DNA double-strand-breaks by homologous recombination (HR), more so than with monotherapy in ARID1AMUT cells. These studies demonstrate BRD4i-ATRi is an effective treatment strategy that capitalizes on synthetic lethality with ARID1A loss in CCOC warranting further study. Citation Format: Yasuto Kinose, Haineng Xu, Sushil Kumar, Hyoung Kim, Sergey Medvedev, Xiaolei Wang, Erin George, Xiaoyin Shan, Sarah Gitto, Kurt D'Andrea, Bradley Wubbenhorst, Margaret Whicker, Dorothy Hallberg, Lauren Schwartz, Katherine L Nathanson, Gordon Mills, Victor E Velculescu, Tian-Li Wang, Eric Brown, Ronny Drapkin, Fiona Simpkins. Dual blockade of BRD4 and the ATR/WEE1 pathway exploits ARID1A loss in clear cell ovarian cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B060.

Proteomic analysis of exosomes secreted during the epithelial-mesenchymal transition and potential biomarkers of mesenchymal high-grade serous ovarian carcinoma

BackgroundThe epithelial-mesenchymal transition (EMT) promotes cell signaling and morphology alterations, contributing to cancer progression. Exosomes, extracellular vesicles containing proteins involved in cell-cell communication, have emerged as a potential source of biomarkers for several diseases.MethodsOur aim was to assess the proteome content of exosomes secreted after EMT-induction to identify potential biomarkers for ovarian cancer classification. EMT was induced in the ovarian cancer cell line CAOV3 by treating it with EGF (10 ng/mL) for 96 h following 24 h of serum deprivation. Subsequently, exosomes were isolated from the supernatant using selective centrifugation after decellularization, and their characteristics were determined. The proteins present in the exosomes were extracted, identified, and quantified using Label-Free-Quantification (LFQ) via Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). To identify potential biomarkers, the obtained proteomic data was integrated with the TGGA database for mRNA expression using principal component analysis and a conditional inference tree.ResultsThe exosomes derived from CAOV3 cells exhibited similar diameter and morphology, measuring approximately 150 nm, regardless of whether they were subjected to EMT stimulation or not. The proteomic analysis of proteins from CAOV3-derived exosomes revealed significant differential regulation of 157 proteins, with 100 showing upregulation and 57 downregulation upon EMT induction. Further comparison of the upregulated proteins with the TCGA transcriptomic data identified PLAU, LAMB1, COL6A1, and TGFB1 as potential biomarkers of the mesenchymal HGSOC subtype.ConclusionsThe induction of EMT, the isolation of exosomes, and the subsequent proteomic analysis highlight potential biomarkers for an aggressive ovarian cancer subtype. Further investigation into the role of these proteins is warranted to enhance our understanding of ovarian cancer outcomes.

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

Diagnostic and Management Challenges of Endometrial Tumours in Developing Countries!

Gynaecological cancers are among the most common cancers in women and hence an important public health issue in very country. Ovarian, Cervical, and Endometrial cancers contribute the most of Gynaecological cancers in India and worldwide. Endometrial benign tumours like Endometrioid cystadenoma/adenofibroma with endometrioid type glands, associated with endometriosis pose challenges of diagnosis. Endometrial cancer (EC) is the most common gynaecological malignancy in the West, but in India, the incidence rates are low. National cancer registry project (NCRP) estimated 27,922 cases of EC in 2022 in India. The possible association between cancer and endometriosis varies according to the histologic subtype of ovarian cancer and is focused mostly on endometroid and clear-cell ovarian cancer subtypes. The only way to diagnose womb cancer for sure is to take a sample of the tissue lining the womb (biopsy) and get histopathology report. However, most of the literate and urban women with ECs present at an early stage due to menorrhagia, abdominal pain or abdominal distension and are associated with a good prognosis. But the situation in rural India is one of lack of diagnostic and management facilities in public sector even at most of the district level. Treatment for endometrial cancer usually involves a hysterectomy, and adjuvant radiotherapy and/or chemotherapy. Surgery sometimes may include the removal of uterus and the fallopian tubes and ovaries, called a Hysterectomy with salpingo-oophorectomy. Adjuvant Radio/Chemotherapy treatment is planned based on final surgical &amp; pathological staging. Due to the lack of cancer awareness, variable pathology, and dearth of proper screening facilities in most developing countries including India, most rural women report at advanced stages, adversely affecting the prognosis and clinical outcomes.

Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo

High-grade serous carcinoma (HGSC) is the most common and aggressive subtype of epithelial ovarian cancer, characterized by gain-of-function TP53 mutations originating in the fallopian tube epithelium. Therapeutic intervention occurs at advanced metastatic disease, due to challenges in early-stage diagnosis, with common disease recurrence and therapy resistance despite initial therapy success. The mevalonate pathway is exploited by many cancers and is potently inhibited by statin drugs. Statins have shown anti-cancer activity in many, but not all cancers. Here, we investigated the role of p53 status in relation to mevalonate pathway signaling in murine oviductal epithelial (OVE) cells and identified OVE cell sensitivity to statin inhibition. We found that p53R175H mutant and Trp53 knockout OVE cells have increased mevalonate pathway signaling compared to p53 wild-type OVE cells. Through orthotopic implantation to replicate the fallopian tube origin of HGSC, p53R175H mutant cells upregulated the mevalonate pathway to drive progression to advanced-stage ovarian cancer, and simvastatin treatment abrogated this effect. Additionally, simvastatin was more efficacious at inhibiting cell metabolic activity in OVE cells than atorvastatin, rosuvastatin and pravastatin. In vitro, simvastatin demonstrated potent effects on cell proliferation, apoptosis, invasion and migration in OVE cells regardless of p53 status. In vivo, simvastatin induced ovarian cancer disease regression through decreased primary ovarian tumor weight and increased apoptosis. Simvastatin also significantly increased cytoplasmic localization of HMG-CoA reductase in ovarian tumors. Downstream of the mevalonate pathway, simvastatin had no effect on YAP or small GTPase activity. This study suggests that simvastatin can induce anti-tumor effects and could be an important inhibitor of ovarian cancer progression.

Development and validation of an individualized gene expression-based signature to predict overall survival of patients with high-grade serous ovarian carcinoma

BackgroundHigh-grade serious ovarian carcinoma (HGSOC) is a subtype of ovarian cancer with a different prognosis attributable to genetic heterogeneity. The prognosis of patients with advanced HGSOC requires prediction by genetic markers. This study systematically analyzed gene expression profile data to establish a genetic marker for predicting HGSOC prognosis.MethodsThe RNA-seq data set and information on clinical follow-up of HGSOC were retrieved from Gene Expression Omnibus (GEO) database, and the data were standardized by DESeq2 as a training set. On the other hand, HGSOC RNA sequence data and information on clinical follow-up were retrieved from The Cancer Genome Atlas (TCGA) as a test set. Additionally, ovarian cancer microarray data set was obtained from GEO as the external validation set. Prognostic genes were screened from the training set, and characteristic selection was performed using the least absolute shrinkage and selection operator (LASSO) with 80% re-sampling for 5000 times. Genes with a frequency of more than 2000 were selected as robust biomarkers. Finally, a gene-related prognostic model was validated in both the test and GEO validation sets.ResultsA total of 148 genes were found to be significantly correlated with HGSOC prognosis. The expression profile of these genes could stratify HGSOC prognosis and they were enriched to multiple tumor-related regulatory pathways such as tyrosine metabolism and AMPK signaling pathway. AKR1B10 and ANGPT4 were obtained after 5000-time re-sampling by LASSO regression. AKR1B10 was associated with the metastasis and progression of several tumors. In this study, Cox regression analysis was performed to create a 2-gene signature as an independent prognostic factor for HGSOC, which has the ability to stratify risk samples in all three data sets (p < 0.05). The Gene Set Enrichment Analysis (GSEA) discovered abnormally active REGULATION_OF_AUTOPHAGY and OLFACTORY_TRANSDUCTION pathways in the high-risk group samples.ConclusionThis study resulted in the creation of a 2-gene molecular prognostic classifier that distinguished clinical features and was a promising novel prognostic tool for assessing the prognosis of HGSOC. RiskScore was a novel prognostic model which might be effective in guiding accurate prognosis of HGSOC.

3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.

Molecular Subtypes of Ovarian Cancer Based on Lipid Metabolism and Glycolysis Reveals Potential Therapeutic Targets

Molecular Subtypes of Ovarian Cancer Based on Lipid Metabolism and Glycolysis Reveals Potential Therapeutic Targets

Prognostic Significance of Programmed Cell Death Ligand 1 Expression in High-Grade Serous Ovarian Carcinoma: A Systematic Review and Meta-Analysis.

(1) Background: High-grade serous ovarian carcinoma (HGSOC) is an aggressive subtype of ovarian cancer. Recent advances have introduced prognostic markers and targeted therapies. Programmed cell death ligand 1 (PD-L1) has emerged as a potential biomarker for HGSOC, with implications for prognosis and targeted therapy eligibility; (2) Methods: A literature search was conducted on major databases, and extracted data were categorized and pooled. Subgroup analysis was performed for studies with high heterogeneity. (3) Results: Data from 18 eligible studies were categorized and pooled based on PD-L1 scoring methods, survival analysis types, and endpoints. The result showed an association between high PD-L1 expression and a favorable prognosis in progression-free survival (HR = 0.53, 95% CI = 0.35-0.78, p = 0.0015). Subgroup analyses showed similar associations in subgroups of neoadjuvant chemotherapy patients (HR = 0.6, 95% CI = 0.4-0.88, p = 0.009) and European studies (HR = 0.59, 95% CI = 0.42-0.82, p = 0.0017). In addition, subgroup analyses using data from studies using FDA-approved PD-L1 antibodies suggested a significant association between favorable prognosis and high PD-L1 expression in a subgroup including high and low stage data in overall survival data (HR = 0.46, 95% CI = 0.3-0.73, p = 0.0009). (4) Conclusions: This meta-analysis revealed a potential association between high PD-L1 expression and favorable prognosis. However, caution is warranted due to several limitations. Validation via large-scale studies, with mRNA analysis, whole tissue sections, and assessments using FDA-approved antibodies is needed.

Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.

Epithelial ovarian cancer (EOC), the most predominant subtype of ovarian cancer (OC), involves poor prognosis and exhibits high aggression. Triptolide (TPL), like other Chinese herbs, has historically played a significant role in modern medicine. The screening system based on Gli-dependent luciferase reporter activity assessed the effects of over 800 natural medicinal materials on hedgehog (Hh) signaling pathway activity and discovered that TPL had an excellent inhibitory effect on Hh signaling pathway activity. However, the significance and mechanism of TPL involvement in regulating the Hh pathway have not been well explored. Thus, this work aimed to understand better how TPL affects the Hh pathway activity, which, in turn, influences the biological behavior of EOC. Our findings observed that Smo agonist SAG-induced EOC cell proliferation, migration, and invasion were drastically reversed by TPL in a concentration-dependent pattern. Further evidence suggested that TPL promotes the degradation of Gli1 and Gli2 to inhibit the activity of the Hh signaling pathway by relying on Gli1 and Gli2 ubiquitination. Our in vivo studies also confirmed that TPL could significantly inhibit the tumor growth of EOC. Taken together, our results revealed that one of the antitumor mechanisms of TPL was the targeted inhibition of the Hh/Gli pathway.

Effect of alpha lipoic acid on epithelial mesenchymal transition in SKOV-3 cells

BackgroundOvarian cancer is the fifth leading cause of cancer-related death in women. Patients are usually diagnosed with advanced tumor metastass. Epithelial over cancer cells spread from primary tumor by undergoing epithelial mesenchymal transition (EMT). It has been suggested that alpha lipoic acid (ALA), a natural antioxidant lipophilic compound, reduces the oxidative stress by causing apoptosis and inhibition of proliferation of cell in cancer cells. The aim of our study was to establish a transforming growth factor β1 (TGF β1) dependent epithelial mesenchymal transition model in the SKOV-3 ovarian adenocarcinoma cell line which is an epithelial subtype of ovarian cancer and to investigate the effects of alpha lipoic acid on EMT and ovarian cancer migration. MethodsFor establish an EMT model, SKOV-3 cells were treated with different dose of TGF β1 and XTT cell viability kit was used to find IC 50 dose of ALA. Four different groups that are control, TGF β1, ALA and ALA + TGF β1 were created. Changes in the expression of genes related to EMT markers that are E-cadherin, vimentin, Snail, Slug, Twist and Zeb were analyzed with quantitative real-time PCR. These proteins were determined with the immunocytochemistry method. The migration capacity was analyzed with wound healing assay. Matrigel invasion capacity test was used to show invasion and colonization test to show colonization. ResultsThe dose of TGF β1 was determined 100 ng/ml at 72 h, the IC50 dose of ALA 219.033 µM at 48 h was determined. EMT markers in the TGF β1 group were compatible with EMT and it was shown to inhibit EMT in the groups given ALA. According to wound healing, colonization and invasion experiments, proliferation and invasion increased in TGF β1 group, but decreased in ALA and combined groups (p < 0.05). ConclusionThese results indicate that ALA suppresses the metastasis of ovarian cancer cells by regulating EMT, implying that ALA might be a potential therapeutic agent for the treatment of ovarian cancer.

Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma

Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and a poor prognosis. In recent years, poly-ADP ribose polymerase (PARP) inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Indisulam (E7070) has been identified as a molecular glue that brings together splicing factor RBM39 and DCAF15 E3 ubiquitin ligase resulting in polyubiquitination, degradation, and subsequent RNA splicing defects. In this work, we demonstrate that the loss of RBM39 induces splicing defects in key DNA damage repair genes in ovarian cancer, leading to increased sensitivity to cisplatin and various PARP inhibitors. The addition of indisulam also improved olaparib response in mice bearing PARP inhibitor-resistant tumors. These findings demonstrate that combining RBM39 degraders and PARP inhibitors is a promising therapeutic approach to improve PARP inhibitor response in ovarian HGSC.

Fallopian tube lesions as potential precursors of early ovarian cancer: a comprehensive proteomic analysis

Ovarian cancer is the leading cause of death from gynecologic cancer worldwide. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype of ovarian cancer. While the origin of ovarian tumors is still debated, it has been suggested that HGSC originates from cells in the fallopian tube epithelium (FTE), specifically the epithelial cells in the region of the tubal-peritoneal junction. Three main lesions, p53 signatures, STILs, and STICs, have been defined based on the immunohistochemistry (IHC) pattern of p53 and Ki67 markers and the architectural alterations of the cells, using the Sectioning and Extensively Examining the Fimbriated End Protocol. In this study, we performed an in-depth proteomic analysis of these pre-neoplastic epithelial lesions guided by mass spectrometry imaging and IHC. We evaluated specific markers related to each preneoplastic lesion. The study identified specific lesion markers, such as CAVIN1, Emilin2, and FBLN5. We also used SpiderMass technology to perform a lipidomic analysis and identified the specific presence of specific lipids signature including dietary Fatty acids precursors in lesions. Our study provides new insights into the molecular mechanisms underlying the progression of ovarian cancer and confirms the fimbria origin of HGSC.

High BMP7 expression is associated with poor prognosis in ovarian cancer.

Bone Morphogenetic Protein 7 (BMP7) is an extracellular signalling protein that belongs to the transforming growth factor-β (TGF- β) superfamily. Previous transcriptomic data suggested that BMP7 expression may be disrupted in ovarian carcinoma and may play an important role in the aggressiveness of the disease. However, the protein expression in patient tumours has not been well studied. The current study aimed to assess BMP7 protein expression in a large cohort of ovarian carcinoma patient tumour samples to establish its associations with different clinical endpoints. Ovarian carcinoma tissue samples from 575 patients who underwent surgery for different subtypes of ovarian cancer were used. BMP7 protein expression was analysed by immunohistochemistry using tissue microarray and full face tumour sections. High BMP7 expression is associated with aggressive ovarian cancer clinicopathological variables including advanced FIGO stage, high grade, residual disease and poor overall survival. Elevated cytoplasmic and nuclear BMP7 expression was significantly associated with advanced FIGO stage, high tumour grade, presence of residual tumours and high-grade serous carcinomas (p = 0.001, 0.005, 0.004, <0.001 and p < 0.001, <0.001, 0.002, 0.001 respectively). Increased cytoplasmic and nuclear BMP7 expression was also significantly associated with an adverse overall survival (p = 0.001 and 0.046 respectively). The study highlights the potential of BMP7 as a prognostic tool and as a potential novel target for ovarian cancer therapies to limit disease progression.

Genetic and pharmacologic dependency upon anti-apoptotic proteins BCL-XL and MCL1 in rare subtypes of ovarian cancer (1259)

Genetic and pharmacologic dependency upon anti-apoptotic proteins BCL-XL and MCL1 in rare subtypes of ovarian cancer (1259)

Identification and validation of a novel anoikis-related signature for predicting prognosis and immune landscape in ovarian serous cystadenocarcinoma

BackgroundOvarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. MethodsThe mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. ResultsWe identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = −0.21, P < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs. ConclusionIn this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients.

Histopathological Types of Ovarian Cancer in Different Age Group of Patients; A Single Institution Experience

Objective: To see the relationship between age and histological types among patients presenting with ovarian cancer at tertiary care hospital, of Karachi Pakistan. Study Design: Cross-sectional study. Place and Duration of study: Department of medical oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan from Mar 2019 to May 2020. Methodology: Three fifty women presenting with confirmed diagnosis of ovarian carcinoma were included irrespective of their age. The information regarding socio-demographics and family history were noted on pre-designed proforma. Pathology reports were obtained from all the patients and information regarding age, stage and histological type were noted. World Health Organization classification was used to classify the histological type of tumours. All data was entered and analyzed using SPSS version 23. Results: The mean age of the study sample was estimated as 44.27±12.7 years ranging from 14-92 years. According to histological type, most of the females had surface epithelial tumors 307(87.71%), followed by sex cord-stromal tumors 20(5.7%) and germ cell tumors tumors 19(5.43%) respectively. The statistically significant difference was observed between age and histological types and subtypes of ovarian cancer (p&lt;0.05). Conclusion: It is concluded that age is an important factor in determining risk of developing different types of ovarian cancers. Serous type of epithelial ovarian cancer is the most common type and commonly present in 4th to 5th decade of life. Germ cell ovarian tumor is second most common type and present in 2nd decade of life.

Identifying high-grade serous ovarian carcinoma-specific extracellular vesicles by polyketone-coated nanowires.

Cancer cell-derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines or patient serum and ascites were analyzed by LC-MS/MS, revealing that both EV subtypes had unique proteomic characteristics. Multivalidation steps identified FRα, Claudin-3, and TACSTD2 as HGSOC-specific sEV proteins, but m/lEV-associated candidates were not identified. In addition, for using a simple-to-use microfluidic device for EV isolation, polyketone-coated nanowires (pNWs) were developed, which efficiently purify sEVs from biofluids. Multiplexed array assays of sEVs isolated by pNW showed specific detectability in cancer patients and predicted clinical status. In summary, the HGSOC-specific marker detection by pNW are a promising platform as clinical biomarkers, and these insights provide detailed proteomic aspects of diverse EVs in HGSOC patients.