Prognostic Biomarker For Ovarian Cancer Research Articles

Expression of PAWR predicts prognosis of ovarian cancer

BackgroundOvarian cancer greatly threatens the general health of women worldwide. Implementation of predictive prognostic biomarkers aids in ovarian cancer management.MethodsUsing online databases, the general expression profile, target-disease associations, and interaction network of PAWR were explored. To identify the role of PAWR in ovarian cancer, gene correlation analysis, survival analysis, and combined analysis of drug responsiveness and PAWR expression were performed. The predictive prognostic value of PAWR was further validated in clinical samples.ResultsPAWR was widely expressed in normal and cancer tissues, with decreased expression in ovarian cancer tissues compared with normal tissues. PAWR was associated with various cancers including ovarian cancer. PAWR formed a regulatory network with a group of proteins and correlated with several genes, which were both implicated in ovarian cancer and drug responsiveness. High PAWR expression denoted better survival in ovarian cancer patients (OS: HR = 0.84, P = 0.0077; PFS, HR = 0.86, P = 0.049). Expression of PAWR could predict platinum responsiveness in ovarian cancer and there was a positive correlation between PAWR gene effect and paclitaxel sensitivity. In 12 paired clinical samples, the cancerous tissues exhibited significantly lower PAWR expression than matched normal fallopian tubes. The predictive prognostic value of PAWR was maintained in a cohort of 50 ovarian cancer patients.ConclusionsHigh PAWR expression indicated better survival and higher drug responsiveness in ovarian cancer patients. PAWR could be exploited as a predictive prognostic biomarker in ovarian cancer.

Soluble heat-shock protein 27 in blood serum is a non-invasive prognostic biomarker for ovarian cancer

ObjectivesOvarian cancer (OC) is the leading cause of death in gynecological oncology, primarily caused by limited prognostic and therapeutic options. The heat shock protein 27 (HSP27) is recognized as a prominent factor in OC, playing a pivotal role in cancer progression machinery such as treatment resistance. Thus, HSP27 may represent an appropriate biomarker for OC diagnosis, prognosis, and therapy response. Materials & methodsExtracellular HSP27 levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples of OC patients (n = 242) and compared to a non-malignant control group without any history of cancer (n = 200). Correlations between serum levels of HSP27 and clinical pathological parameters were analyzed by bivariate analysis. Survival analyses were carried out by Kaplan-Meier test. ResultsThis study demonstrated that protein levels of HSP27 are comparable in the blood serum of healthy women and OC patients. However, HSP27 levels are significantly correlated with the volume of ascites, residual tumor mass, and age at first diagnosis in OC patients. Notably, elevated levels of HSP27 demonstrate significantly higher overall survival. ConclusionTaken together, our findings demonstrate that high levels of circulating HSP27 in serum are associated with improved overall survival of OC patients. Even though functionality of secreted HSP27 is still unclear, serum levels of HSP27 represent a putative non-invasive prognostic biomarker candidate for OC progression.

Integrative network analysis identifies an immune-based prognostic signature as the determinant for the mesenchymal subtype in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) has been classified into four molecular subtypes, of which the mesenchymal subtype has the poorest survival. Our goal is to develop an immune-based prognostic signature by incorporating molecular subtypes for EOC patients. The gene expression profiles of EOC samples were collected from seven public datasets as well as an internal retrospective validation cohort, containing 1192 EOC patients. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for EOC (IPSEOC). The signature was trained and validated in eight independent datasets. Seven immune genes were identified as key regulators of the mesenchymal subtype and were used to construct the IPSEOC. The IPSEOC significantly divided patients into high- and low-risk groups in discovery (OS: P < .0001), 6 independent public validation sets (OS: P = .04 to P = .002), and an internal retrospective validation cohort (OS: P = .025). Furthermore, pathway analysis revealed that differences between risk groups were mainly activation of mesenchymal-related signalling. Moreover, a significant correlation existed between the IPSEOC values versus clinical phenotypes including late tumor stages, drug resistance. We propose an immune-based signature, which is a promising prognostic biomarker in ovarian cancer. Prospective studies are needed to further validate its analytical accuracy and test the clinical utility.

Preoperative low hematocrit is an adverse prognostic biomarker in ovarian cancer.

The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan-Meier method and log-rank test. 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050-2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7months in patients with preoperative HCT ≥ 35% and 61.7months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65years, BMI ≥ 25.0kg/m2, ascites volume ≤ 500mL, ASA score < 3, albumin ≥ 35g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110g/mL), low albumin (< 35g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. Preoperative low HCT was a valuable predictor for EOC patients' poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.

H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival.

Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of H2AX expression to compare OS and perform gene set enrichment. qRT-PCR validated in-silico H2AX findings followed by immunohistochemistry on a tissue microarray. The association between single nucleotide polymorphisms in the area of H2AX; prevalence and five-year OC survival was tested in samples from the UK Biobank. Results: H2AX was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (p = 0.010). Gene Set Enrichment Analysis demonstrated gene sets involved in G2/M checkpoint, DNA repair mTORC1 signalling were enriched in the H2AX highly expressing OCs. Polymorphisms in the area around the gene were associated with both OC prevalence (rs72997349-C, p = 0.005) and worse OS (rs10790282-G, p = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. Conclusions: Our findings suggest that H2AX can be a novel prognostic biomarker for OC.

Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors.

Background: Lymphocyte telomere length is strongly correlated with patient prognosis in several malignant tumor types and is thought to be related to tumor immunity. However, this correlation has not been studied in gynecological cancers. We determined the prognostic significance of peripheral blood lymphocyte telomere length in gynecologic cancers. Methods: Telomere length of lymphocytes from patients with gynecological malignant tumors (ovarian cancer (OC), N = 72; cervical cancer (CC), N = 63; endometrial cancer (EC), N = 87) was examined by quantitative reverse-transcription PCR of isolated mononuclear cells. Kaplan–Meier and Cox proportional hazard analyses were used to determine the association between lymphocyte telomere length and clinicopathological factors. Results: The overall survival (OS) and progression-free survival (PFS) of patients were based on the dichotomized lymphocyte telomere length using the median as a threshold (OC: 0.75, CC: 1.94, and EC: 1.09). A short telomere length was significantly correlated with residual tumors (≥1 cm) in OC and with advanced stage (III and IV) of CC. In OC and CC, patients with shorter relative lymphocyte telomere length (RLT) had significantly poorer OS and PFS than patients with longer RLT (p = 0.002, p = 0.003, and p = 0.001, p = 0.001, respectively). However, in EC, RLT was not significantly associated with OS or PFS (p = 0.567 and p = 0.304, log-rank test). Multivariate analysis showed that shorter RLT was a significant independent prognostic factor of PFS and OS for OC (p = 0.03 and p = 0.04, respectively) and CC (p = 0.02 and p = 0.03, respectively). Conclusions: Patients with OC and CC with shorter lymphocyte telomeres have significantly reduced survival; therefore, the peripheral blood lymphocyte telomere length is a prognostic biomarker in OC and CC.

Co-expressed functional module-related genes in ovarian cancer stem cells represent novel prognostic biomarkers in ovarian cancer

ABSTRACT Ovarian cancer is the leading cause of death from gynecologic malignancies. Cancer stem cells (CSC) seem to play a crucial role in tumor metastasis, recurrence, and chemoresistance. Therefore, CSCs offer significant potential for developing therapeutic targets and to understand tumor recurrence and chemoresistance mechanisms. In the present study, our aim was the identification of the gene group in ovarian CSCs (O-CSCs) and the potential of the resultant gene group in ovarian cancer prognosis. Two different microarray data sets were analyzed by comparing gene expression levels between O-CSCs and cancer samples. The O-CSC co-expression network was reconstructed and its modules were identified. According to the analysis results, 74 mutual DEGs were identified. The O-CSC-specific co-expression network included 32 nodes and 95 edges (network density: 19%), while the co-expression network in cancer samples was reconstructed with 74 nodes and 1066 edges (network density: 39%). Understanding of the molecular mechanism and signatures of O-CSCs should provide valuable insight into chemotherapy resistance and recurrence of ovarian tumors. A highly connected 12 gene module in O-CSC samples of BAMB1, NFKB12, EZR, TNFAIP3, C1orf86, PMAIP1, GEM, KHDRBS3, FILIP1, FGFR2, TGFBR3 and PEG10, (network density: 67%) was identified. Prognostic performance of these genes was evaluated independently using six ovarian cancer datasets (n = 1933 patient samples) via survival analysis. These co-expressed genes were determined as prognostic targets in ovarian cancer. Through literature search validation, five genes (C1orf86, PMAIP1, FILIP1, NFKB12 and PEG10) suggested as novel molecular targets in ovarian cancer. The presented prognostic biomarkers here provide a resource for the understanding of tumor recurrence and chemoresistance and may facilitate critical research directions and development of new prognostic and therapeutic strategies for ovarian cancer. Abbreviations CSCs: cancer stem cells; O-CSCs: ovarian CSCs; FACS: fluorescence-activated cell sorting; SP: side population; MP: main population; TFs: transcription factors.

MiR-194-5p inhibits SLC40A1 expression to induce cisplatin resistance in ovarian cancer

BackgroundmiR-194-5p has been associated with drug resistance in many cancers. However, the role of miR-194-5p in cisplatin resistance in ovarian cancer is still unclear. Materials and methodsTo study the role and mechanism of miR-194-5p in cisplatin resistance, qRT-PCR was performed to determine the expression of miR-194-5p and SLC40A1 in ovarian cancer. Cell Counting Kit-8 (CCK8) assay was used to analyse cell viability after cisplatin treatment. Dual-luciferase reporter gene assay was performed to examine the relationship between miR-194-5p and SLC40A1. The genes downstream of SLC40A1 were investigated through bioinformatics analysis. ResultsCompared to cisplatin-sensitive ovarian cancer cells, higher miR-194-5p expression and lower SLC40A1 expression were found in cisplatin-resistant ovarian cancer cells. Moreover, this study demonstrated that over-expression of miR-194-5p inhibited SLC40A1 expression, and knockdown of miR-194-5p promoted SLC40A1 expression. In addition, dual-luciferase reporter gene assay further confirmed the negative correlation between miR-194-5p and SLC40A1. Furthermore, we found that over-expression of miR-194-5p resulted in cisplatin resistance. When miR-194-5p and SLC40A1 were simultaneously up-regulated, cisplatin sensitivity increased, while down-regulation of miR-194-5p sensitised ovarian cancer cells to cisplatin. However, when miR-194-5p and SLC40A1 were simultaneously down-regulated, cisplatin sensitivity was decreased. These data suggested that miR-194-5p inhibited SLC40A1 expression to induce cisplatin resistance. In addition, bioinformatics analysis indicated a positive correlation of SLC40A1 with hephaestin (HEPH), and homeostatic iron regulator (HFE). However, we found that HEPH and HFE were associated with cisplatin resistance, suggesting that their role in drug resistance is induced by miR-194-5p/SLC40A1. ConclusionIn conclusion, we found that miR-194-5p inhibited SLC40A1 expression to induce cisplatin resistance in ovarian cancer. This study suggests that miR-194-5p could be a potential therapeutic target and a prognostic biomarker for ovarian cancer, with important implications for future research.

Response to comments on "Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer".

Response to comments on "Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer".

Comment on "Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer," Cancer Lett. 2020 Jan 2; 473 (2020) 139-147.

Comment on "Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer," Cancer Lett. 2020 Jan 2; 473 (2020) 139-147.

Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer.

Ovarian cancer (OC), one of the gynecologic malignancies with high invasive and metastatic potential, has a low survival rate in females. Although cytoreductive surgery combined with chemotherapy is the principal treatment for OC, the prognosis remains poor, and the recurrence rate of OC remains high. It is urgent to explore novel biomarkers for the diagnosis and prognosis of OC, as well as therapeutic targets. Circular RNAs (circRNAs) are a class of highly conserved, stable and abundant noncoding RNAs (ncRNAs). Recent studies have shown that circRNAs participate in OC progression by regulating various processes, including cell proliferation, migration, invasion and apoptosis. In addition, circRNAs are potential biomarkers for OC diagnosis and prognosis. This review provides an overview of recent findings on circRNAs in OC, including their functions and molecular mechanisms, and discusses their potential roles as diagnostic and prognostic biomarkers, as well as therapeutic targets for OC.

Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma.

The programmed cell death 1/programmed cell death 1 ligand 1 pathway was successfully targeted in cancer immunotherapy. Elevated interleukin‐17 (IL‐17), which is known in autoimmune diseases, has recently been recognized in cancer patients. We investigated the role of IL‐17 in the regulation of expression of programmed cell death 1 ligand 1 in ovarian cancer by evaluating changes in the number of IL‐17‐producing cluster of differentiation 4 helper T cells (Th17) and γδT cells (γδT17) in PBMC of 52 gynecological cancer patients (including 30 ovarian cancer patients) and 18 healthy controls. The occupancy ratio of Th17 and γδT17 was higher in ovarian cancer and endometrial cancer patients than in controls, determined by multi‐color flow cytometry (Th17: P < 0.0001 and P = 0.0002, respectively; γδT17: P = 0.0020 and P = 0.0084, respectively). IL‐17 mRNA level was elevated in PBMC of ovarian cancer patients (P = 0.0029), as measured by RT‐PCR. The neutrophil‐to‐lymphocyte ratio, which is a prognostic biomarker of ovarian cancer, correlated with Th17 occupancy ratio in patients (P = 0.0068). We found that programmed cell death 1 ligand 1 expression and its associated factors (IL‐6 and phospho‐signal transducer and activator of transcription 3) were induced by IL‐17 in an ovarian cancer cell line. These results suggest that increased Th17 counts and IL‐17 level, which correlated with high neutrophil‐to‐lymphocyte ratio and programmed cell death 1 ligand 1 expression, are potential biomarkers for poor prognosis in ovarian cancer and likely indications for application of programmed cell death 1 ligand 1 pathway inhibitors.

Prognostic value of lymphocyte-to-monocyte ratio in ovarian cancer: A meta-analysis.

Lymphocyte-to-monocyte ratio (LMR) was recently proposed as a prognostic factor of ovarian cancer. However, prognostic value of the LMR in ovarian cancer remains inconclusive. The study aimed to assess prognostic value of the LMR in ovarian cancer. Seven common databases were comprehensively searched for relevant studies. The analyses were performed for overall survival (OS), progression-free survival (PFS) and clinical parameters. The hazard ratio (HR) and 95% confidence interval (CI) were used to analyze OS and PFS. A total of 2343 patients with ovarian cancer were included in this meta-analysis. The results showed that a low LMR predicted shorter OS (HR = 1.81, 95% CI = 1.38-2.37, P < .01) and PFS (HR = 1.65 95% CI = 1.46-1.85, P < .01) when compared to a high LMR in ovarian cancer. Besides, a low LMR was significantly associated with advanced clinical stage (P < .01), earlier lymph node metastasis (P = .01), higher carbohydrate antigen-125 levels (P < .01), larger residual tumor (P < .01) and worse chemosensitivity (P < .01) when compared to a high LMR in ovarian cancer. Low LMR was associated with unfavorable survival in patients with ovarian cancer. LMR could serve as a prognostic biomarker of ovarian cancer.

Ascites-Derived Extracellular microRNAs as Potential Biomarkers for Ovarian Cancer.

Ovarian cancer as the most fatal gynecological malignancy is often manifested by excessive fluid accumulation known as ascites or effusion. Ascites-derived microRNAs (miRNAs) may be closely associated with ovarian cancer progression. However, our knowledge of their roles, altered expression, and clinical outcomes remained limited. In this study, large-scale expression profiling of 754 human miRNAs was performed using real-time quantitative polymerase chain reaction and 384-well TaqMan array human miRNA A and B cards to identify differentially expressed miRNAs between extracellular fraction of the ascitic fluid associated with high-grade serous ovarian carcinomas and control plasma. Of the 754 miRNAs, 153 were significantly differentially expressed relative to the controls. Expression of 7 individual miRNAs (miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-1290, and miR-30a-5p) was further validated in extended sample sets, including serous, endometrioid, and mucinous subtypes. All miR-200 family members and miR-1290 were conspicuously overexpressed, while miR-30a-5p was only weakly overexpressed. The ability of miRNAs expression to discriminate the pathological samples from the controls was strong. Receiver operating characteristic curve analyses found area under the curve (AUC) values of 1.000 for miR-200a, miR-200c, miR-141, miR-429, and miR-1290 and of AUC 0.996 and 0.885 for miR-200b and miR-30a-5p, respectively. Preliminary survival analyses indicated low expression level of miR-200b as significantly related to longer overall survival (hazard ratio [HR]: 0.25, mean survival 44 months), while high expression level was related to poor overall survival (HR: 4.04, mean survival 24 months). Our findings suggested that ascites-derived miRNAs should be further explored and evaluated as potential diagnostic and prognostic biomarkers for ovarian cancer.

Proteomics profiling of plasma exosomes in epithelial ovarian cancer: A potential role in the coagulation cascade, diagnosis and prognosis.

Ovarian cancer remains the most lethal type of cancer among all gynecological malignancies. The majority of patients are diagnosed with ovarian cancer at the late stages of the disease. Therefore, there exists an imperative need for the development of early ovarian cancer diagnostic techniques. Exosomes, secreted by various cell types, play pivotal roles in intercellular communication, which emerge as promising diagnostic and prognostic biomarkers for ovarian cancer. In this study, we present for the first time, at least to the best of our knowledge, the proteomics profiling of exosomes derived from the plasma of patients with ovarian cancer via liquid chromatography tandem mass spectrometry (LC-MS/MS) with tandem mass tagging (TMT). The exosomes enriched from patient plasma samples were characterized by nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), transmission electron microscopy (TEM) and western blot analysis. The size of the plasma exosomes fell into the range of 30 to 100 nm in diameter. The exosomal marker proteins, CD81 and TSG101, were clearly stained in the exosome samples; however, there was no staining for the endoplasmic reticulum protein, calnexin. A total of 294 proteins were identified with all exosome samples. Among these, 225 proteins were detected in both the cancerous and non-cancerous samples. Apart from universal exosomal proteins, exosomes derived from ovarian cancer patient plasma also contained tumor-specific proteins relevant to tumorigenesis and metastasis, particularly in epithelial ovarian carcinoma (EOC). Patients with EOC often suffer from coagulation dysfunction. The function of exosomes in coagulation was also examined. Several genes relevant to the coagulation cascade were screened out as promising diagnostic and prognostic factors that may play important roles in ovarian cancer progression and metastasis. On the whole, in this study, we successfully isolated and purified exosomes from plasma of patients with EOC, and identified a potential role of these exosomes in the coagulation cascade, as well as in the diagnosis and prognosis of patients. differentially expressed genes, functional enrichment analysis, protein-protein interaction, diagnostic and prognostic biomarkers

Serum CA125 levels are decreased in rectal cancer but increased in fibrosis-associated diseases and in most types of cancers.

CA125 is a heavily glycosylated protein and was first identified as an ovarian cancer antigen in 1981 that is recognized by a monoclonal antibody generated by the hybridoma technique. The increased serum CA125 levels detected by the monoclonal antibodies were subsequently developed into a diagnostic or prognostic biomarker for ovarian cancer. Generally, the cutoff value of serum CA125 level is 35U/mL to indicate potential cancer risk. However, the specificity and sensitivity of CA125 are not satisfactory in clinical applications, especially for early diagnosis of ovarian cancer. Moreover, elevated serum CA125 levels have been observed in a variety of cancer and noncancer diseases. In the current study, a total of 41,830 clinical lab test results of serum CA125 levels from healthy individuals and patients with 40 different types of diseases during the past 5 years were retrieved and analyzed. We found that the median values of serum CA125 levels were higher in patients with cirrhosis (52.34U/mL), lung fibrosis (52.04U/mL), nephrotic syndrome (31.24U/mL), and pancreatic cancer (27.06U/mL) than that in ovarian cancer patients (18.61U/mL) with statistical significance (Mann-Whitney test, p<0.0001). Moreover, healthy individuals >65 years old and patients suffering rectal cancer, cerebrovascular disease, and gastritis had significantly low serum CA125 levels compared to that of the healthy individuals. Thus, serum CA125 levels were either increased or decreased in both cancer and noncancer diseases. Based on these data and the accumulating evidence, we proposed that the abnormal serum CA125 levels might be associated with pathological changes in different organs and tissues induced by specific disease.

Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer

Ovarian cancer is a heterogeneous malignancy that poses tremendous clinical challenge. Based on unsupervised classification of whole-genome gene expression profiles, four molecular subtypes of ovarian cancer were recently identified. However, single-driver molecular events specific to these subtypes have not been clearly elucidated. We aim to characterize the regulatory mechanisms underlying the poor prognosis mesenchymal subtype of ovarian cancer using a systems biology approach, involving a variety of molecular modalities including gene and microRNA expression profiles. miR-508-3p emerged as the most powerful determinant that regulates a cascade of dysregulated genes in the mesenchymal subtype, including core genes involved in epithelial–mesenchymal transition (EMT) program. Moreover, miR-508-3p down-regulation, due to promoter hypermethylation, was directly correlated with metastatic behaviors in vitro and in vivo. Taken together, our multidimensional network analysis identified miR-508-3p as a master regulator that defines the mesenchymal subtype and provides a novel prognostic biomarker to improve management of this disease.

Transcription factors WT1 and p53 combined: a prognostic biomarker in ovarian cancer

BackgroundNew approaches to ovarian cancer are needed to improve survival. Wilms’ tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical significance of the combined expression of these two transcription factors has not been studied.MethodsOne hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan–Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival.ResultsWT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40.ConclusionsWT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.

Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

Activity of the voltage-gated Nav1.5 sodium channel has been reported to be involved in cell proliferation, cancer invasion and gene expression. In addition, eicosapentaenoic acid(EPA) has recently been suggested to inhibit ovarian cancer cell growth and suppress tumor metastasis. The present study aimed to explore the association between EPA, the Nav1.5 sodium channel and ovarian cancer cells. Using patch-clamp technique and RNA interference approaches, sodium currents were recorded in epithelial ovarian cancer cells, and it was confirmed that the Nav1.5 channel carried the sodium currents. Furthermore, EPA effectively inhibited sodium currents in a dose-dependent manner, shifted the steady-state inactivation curve of sodium currents to the hyperpolarizing direction and reduced sodium window currents. In addition, EPA induced a shift in the inactivation curve in a dose-dependent manner. Inhibition of the sodium channel, either by EPA or by Nav1.5 knockdown, attenuated ovarian cancer cell migration and proliferation. To the best of our knowledge, the present study is the first to conduct sodium current recording in ovarian cancer cells, and revealed that EPA may inhibit Nav1.5-mediated ovarian cancer cell migration and growth. These findings not only present a potential prognostic biomarker for ovarian cancer, but also provide a strategytowards the development of novel pharmacological treatments for patients with ovarian cancer.

IL-6 and VEGF-A, novel prognostic biomarkers for ovarian cancer?

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer in the Western world with a 5-year survival rate of <30% (1). One reason for the EOC high mortality is related to its unusual mechanism of dissemination. Cells detach from the primary tumor site and then aggregate to form free-floating multicellular spheroids.