Biomarker For Epithelial Ovarian Cancer Research Articles

Analysis of the association between KIN17 expression and the clinical features/prognosis of epithelial ovarian cancer, and the effects of KIN17 in SKOV3 cells.

DNA double-strand breaks (DSBs) are an important mechanism of chemotherapy in epithelial ovarian cancer (EOC). Kin17 DNA and RNA binding protein (KIN17) serves a crucial role in DSB repair. In the present study, the association between KIN17 and EOC, and the effects of KIN17 on EOC cells in vitro were evaluated. A bioinformatics method was used to determine the mRNA expression levels of KIN17 in EOC and its association with EOC prognosis including overall survival (OS) and progression free survival (PFS) time. Western blotting and immunohistochemical staining were used to evaluate the expression levels of KIN17 in EOC samples. Kaplan-Meier and Cox regression analyses were utilized to analyze risk factors for the OS of patients with EOC. A Cell Counting Kit-8 assay was performed to explore the roles of KIN17 in SKOV3 cells. Both the transcription and expression of KIN17 were upregulated in EOC tissues. Furthermore, the OS of patients with EOC with high mRNA expression levels of KIN17 was shorter than that of patients with EOC with low expression levels. High KIN17 expression was an independent risk factor for EOC prognosis. Furthermore, KIN17 knockdown inhibited the proliferation of SKOV3 cells, enhanced the sensitivity of the cells to cisplatin and inhibited the migration ability of the cells. These results suggested that KIN17 may act as an ideal candidate for therapy and as a prognostic biomarker of EOC, although the underlying mechanisms require further exploration.

ARRDC3 as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer Based on Data Mining.

PurposeThe dysregulation of arrestin domain containing 3 (ARRDC3) has an important effect on oncogenesis and tumor progression in many cancers, including renal cell carcinoma and breast cancer. However, the role of ARRDC3 in ovarian cancer (OC) has not been reported.MethodsThe present study explored the diagnostic and prognostic roles of ARRDC3 in ovarian cancer using GEPIA, ONCOMINE, GEO, and Kaplan–Meier Plotter databases for training and validation. Then, we conducted a stratified analysis for clinicopathological factors using Kaplan–Meier Plotter and GEPIA databases. To further explore the mechanisms, we also used the MIST database to visualize the protein–protein interaction network of ARRDC3 associated with OC. The gene–gene interaction network was visualized by GeneMANIA plugin in Cytoscape 3.8.0 software, and the associated co-expression genes of ARRDC3 were analyzed by the cBioPortal database. The 100 top co-expression genes chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used by the DAVID website.ResultsA significant difference in ARRDC3 mRNA expression was found between OC and normal ovary tissues. ARRDC3 could potentially be implicated in the diagnosis of OC. A high ARRDC3 mRNA expression level was associated with poor overall survival and progression-free survival. However, no significance was reported in respect to post progression survival. Except for histology, which had no prognostic value for PPS in stratified analysis, stratified analysis of other factors had prognostic value for OS, PFS, and PPS. Interestingly, we found a positive correlation between ARRDC3 expression and CD8+ T cells, macrophages, neutrophils, and dendritic cells, indicating that ARRDC3 might be associated with immune infiltration of these immune cells. Co-expression genes enrichment analysis found that they were involved in the Renin-angiotensin system pathway.ConclusionDifferentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.

A Study of CD44 Positive Cancer Cells in Epithelial Ovarian Cancer and their Correlation with P53 And Ki67.

Context Epithelial ovarian carcinomas are one of the most common lethal gynecological malignancies. There is no specific symptom or biomarker for detection of this malignancy in early stage. So, the advanced stage, nature of frequent recurrences, and resistance to chemotherapies make it very difficult to deliver proper treatment to patients. Efforts are on to identify the presence of cancer stem cell by using a specific biomarker in epithelial ovarian cancer in the early stage. Objectives This study aims to identify the CD44 positive cancer cells in epithelial ovarian carcinoma of different histopathological types. It also intends to correlate the expression of CD44 with the expression of p53 and Ki67. Materials and Methods Sections from diagnosed specimens of ovarian epithelial neoplasm had been fixed in 10% formalin and embedded in paraffin, and they were used for immunohistochemical (IHC) staining for CD44, p53, and Ki67, using a peroxidase kit with mouse monoclonal antibodies. Then, the slides were evaluated for both tumor cell percentage and intensity of immunoreactivity. Statistical Analysis Chi-square had been used to find the significance of study. Significance level was considered at p value < 0.05 Results In this study, 40 patients were included in a period of one and a half years. The present study suggested that the levels of CD44 expression were increased in epithelial ovarian cancer compared to borderline tumor. CD44 was positively correlated with the ki67 expression and tumor grade. High-grade serous, mucinous, and endometrioid tumors were associated with high CD44 expression. Positivity of CD44 was found significantly higher in case of positive status of p53 (z = 3.65; p < 0.0001). Conclusion We can correlate CD44 positive cancer stem cells with grade of ovarian carcinomas, but for prognostic significance and therapeutic applications, more corroborative and multicentric works in this field are needed. CD44 can be targeted for therapy in recurrent and resistant cases of ovarian cancer.

The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia.

MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally, it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.

Cytokines as Prognostic Biomarkers of Epithelial Ovarian Cancer (EOC): A Systematic Review and Meta-Analysis.

Objectives:The value of cytokines as epithelial ovarian cancer (EOC) prognostic factors has been widely investigated. This study aimed to determine the role of single cytokine as a biomarker prognosis in EOC. Materials and Methods:We conducted a systematic review and meta-analysis of studies reporting cytokine as the prognostic predictor in EOC based on PRISMA guideline. We included English articles investigating associations of preoperative cytokines level in tissue, blood or ascites with overall survival (OS) or disease-free survival (DFS) from PUBMED and EBSCO. Summary hazard ratios (HRs) and confidence intervals (CIs) were calculated. Results: Fifty studies investigating twenty types of cytokines in tumor tissue, serum, and ascites from 5,376 patients were included. Pre-operative high VEGF level was associated with poor OS (HR 2.28, 95%CI [1.28, 3.28]) and DFS (HR 2.13, 95%CI [1.63, 2.78]) in serum and OS (HR 1.80, 95%CI [1.45, 2.23]) in tissue. IL-6 level in blood was associated with DFS (HR 1.60, 95%CI [1.21, 2.11]). There was no single cytokine which investigated by at least 2 studies reporting hazard ratio in ascites, so we did not conduct the meta-analysis. Other cytokines (serum IL-8; ascites fluid IL-8, IL-10, IFN-γ, TNF-α; and ovarian tissue TGF-α, CSF-1, IL-10 ,TGF-β1, IL-17) associated with the poorer prognosis, could not be pooled due to lack of studies. Conclusion: Pre-operative VEGF level in serum and tissue specimen seem to be the potential candidate of an unfavorable prognostic biomarker for EOC. The evidence was lacking to support the other cytokines investigated in blood, tissue and ascites as prognostic biomarkers for EOC.

Disregulations of PURPL and MiR-338-3p Could Serve As Prognosis Biomarkers for Epithelial Ovarian Cancer.

Objective: The present study aimed to explore the expressions of long noncoding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL) in different ovarian tissues, and to evaluate the significance of disregulations of PURPL and microRNA-338-3p (miR-338-3p) in epithelial ovarian cancer (EOC).Methods: The expressions of PURPL in ovarian cancer, the relations between PURPL and the prognosis of ovarian cancer, and the relation between PURPL and miR-338-3p were queried in multiple biomedical databases. Real-time PCR was performed to detect the expressions of PURPL in different ovarian tissues. Logistic regression analysis was used to analyze the risk factors of recurrence and death. Kaplan-Meier analysis was implemented to evaluate the relations between PURPL and miR-338-3p expressions and the survival of ovarian cancer.Results: PURPL could target miR-338-3p, PURPL were upregulated in ovarian cancer tissues, upregulation of PURPL in ovarian cancer was negatively related with the recurrence free survival (RFS) and overall survival (OS), which were indicated by biomedical databases query. Our data showed upregulations of PURPL were noted in ovarian cancer tissues. Higher expressions of PURPL were associated with more advanced FIGO stage and developed lymph node metastasis in epithelial ovarian cancer. Upregulation of PURPL was related with the recurrence (P=0.002, OR=21.482, 95%CI: 3.457~94.251) and death (P=0.004, OR=35.643, 95%CI: 2.453~84.359) of ovarian cancer patient. PURPL expressions were negatively correlated to miR-338-3p expressions in different ovarian tissues (r = -0.968, P<0.0001). Poor RFS (χ2=19.410, P=0.0002) and OS (χ2=17.600, P=0.0005) were found in patients with high level PURPL and low level miR-338-3p expressions.Conclusions: Upregulation of PURPL and downregulation of miR-338-3p were related with the poor RFS and OS of ovarian cancer, which indicated disregulations of PURPL and miR-338-3p could serve as prognosis biomarkers for epithelial ovarian cancer.

Long non-coding RNA SNHG25 promotes epithelial ovarian cancer progression by up-regulating COMP.

Long non-coding RNAs (lncRNAs) play a pivotal role in the genesis and development of cancer. The role and molecular mechanisms of SNHG25 in epithelial ovarian cancer (EOC) have not been investigated. In the present study, we showed that SNHG25 expression was up-regulated in EOC tissues relative to normal ovarian tissues. In vitro, functional experiments demonstrated that high expression of SNHG25 promoted proliferation, migration and invasion, and decreased apoptosis, in ovarian cancer cell lines. In vivo, downregulation of SNHG25 inhibited the growth (tumor volume) of subcutaneous xenografts in nude mice. High-throughput sequencing and western blot analysis showed a significant decrease in the expression of COMP mRNA and protein in SNHG25 knockdown compared to control ovarian cancer cells. These data suggest that SNHG25 promotes EOC progression by regulating COMP, serving as a potential biomarker for EOC.

Expression of Circulating MicroRNA-141 in Epithelial Ovarian Cancer.

BackgroundEpithelial ovarian cancer (EOC) is a lethal disease due to late diagnosis and lack of effective screening methods. MicroRNA (miR/miRNA) plays an important role in ovarian carcinogenesis and may serve as a non-invasive biomarker for EOC. This study aimed to assess miR-141 expression in the blood plasma of patients with EOC and healthy subjects and determine its association with the clinical stage of EOC.MethodsThis cross-sectional study used blood plasma from 30 newly diagnosed untreated patients with EOC and 25 healthy subjects. The mean age was 47.73 (SD = 10.29) years for EOC and 44.48 (SD = 16.14) years for healthy subject. The total RNA was isolated from blood plasma and reversed transcribed to obtain cDNA. The expression of miR-141 was measured by real-time quantitative polymerase chain reaction (qRT-PCR), and calculated using 2−ΔΔCt methods. The data were analysed using Mann-Whitney test.ResultsThe expression of miR-141 was upregulated 8.41 fold in the blood plasma of EOC patients compared to healthy controls (P < 0.001). Expression of miR-141 in the advanced stage was upregulated 4.2 fold compared to the early stage (P < 0.001).ConclusionThe miR-141 was upregulated in the blood plasma of EOC and associated with an advanced stage of disease, suggesting it has potential as a biomarker for EOC detection.

The Emerging Role of CD24 in Cancer Theranostics-A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond.

Complete cytoreductive surgery is the cornerstone of the treatment of epithelial ovarian cancer (EOC). The application of fluorescence image-guided surgery (FIGS) allows for the increased intraoperative visualization and delineation of malignant lesions by using fluorescently labeled targeting biomarkers, thereby improving intraoperative guidance. CD24, a small glycophosphatidylinositol-anchored cell surface receptor, is overexpressed in approximately 70% of solid cancers, and has been proposed as a prognostic and therapeutic tumor-specific biomarker for EOC. Recently, preclinical studies have demonstrated the benefit of CD24-targeted contrast agents for non-invasive fluorescence imaging, as well as improved tumor resection by employing CD24-targeted FIGS in orthotopic patient-derived xenograft models of EOC. The successful detection of miniscule metastases denotes CD24 as a promising biomarker for the application of fluorescence-guided surgery in EOC patients. The aim of this review is to present the clinical and preclinically evaluated biomarkers for ovarian cancer FIGS, highlight the strengths of CD24, and propose a future bimodal approach combining CD24-targeted fluorescence imaging with radionuclide detection and targeted therapy.

Genetically predicted circulating protein biomarkers and ovarian cancer risk

ObjectiveMost women with epithelial ovarian cancer (EOC) are diagnosed after the disease has metastasized and survival in this group remains poor. Circulating proteins associated with the risk of developing EOC have the potential to serve as biomarkers for early detection and diagnosis. We integrated large-scale genomic and proteomic data to identify novel plasma proteins associated with EOC risk. MethodsWe used the germline genetic variants most strongly associated (P <1.5 × 10−11) with plasma levels of 1329 proteins in 3301 healthy individuals from the INTERVAL study to predict circulating levels of these proteins in 22,406 EOC cases and 40,941 controls from the Ovarian Cancer Association Consortium (OCAC). Association testing was performed by weighting the beta coefficients and standard errors for EOC risk from the OCAC study by the inverse of the beta coefficients from INTERVAL. ResultsWe identified 26 proteins whose genetically predicted circulating levels were associated with EOC risk at false discovery rate < 0.05. The 26 proteins included MFAP2, SEMG2, DLK1, and NTNG1 and a group of 22 proteins whose plasma levels were predicted by variants at chromosome 9q34.2. All 26 protein association signals identified were driven by association with the high-grade serous histotype that comprised 58% of the EOC cases in OCAC. Regional genomic plots confirmed overlap of the genetic association signal underlying both plasma protein level and EOC risk for the 26 proteins. Pathway analysis identified enrichment of seven biological pathways among the 26 proteins (Padjusted <0.05), highlighting roles for Focal Adhesion-PI3K-Akt-mTOR and Notch signaling. ConclusionThe identified proteins further illuminate the etiology of EOC and represent promising new EOC biomarkers for targeted validation by studies involving direct measurement of plasma proteins in EOC patient cohorts.

Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted. We performed intraoperative blood sampling from ovarian veins of stage I epithelial ovarian carcinomas and analyzed the serum proteome. Junction plakoglobin (JUP) was found to be elevated in venous blood from ovaries with malignancies when compared to those with benign disease. Peripheral plasma JUP levels were validated by ELISA in a multicenter international patient cohort. JUP was significantly increased in FIGO serous stage IA+B (1.97-fold increase; p < 0.001; n = 20), serous stage I (2.09-fold increase; p < 0.0001; n = 40), serous stage II (1.81-fold increase, p < 0.001, n = 23) and serous stage III ovarian carcinomas (1.98-fold increase; p < 0.0001; n = 34) vs. normal controls (n = 109). JUP plasma levels were not increased in early stage breast cancer (p = 0.122; n = 12). In serous ovarian cancer patients, JUP had a sensitivity of 85% in stage IA+B and 60% in stage IA-C, with specificities of 76 and 94%, respectively. A logistic regression model of JUP and Cancer Antigen 125 (CA125) revealed a sensitivity of 70% for stage IA+B and 75% for stage IA-C serous carcinomas at 100% specificity. Our novel ovarian blood sampling – proteomics approach identified JUP as a promising new biomarker for epithelial ovarian cancer, which in combination with CA125 might fulfill the test criteria for ovarian cancer screening.

B7-H7 is a prognostic biomarker in epithelial ovarian cancer.

BackgroundB7-H7 is a newly identified member of the B7 immune checkpoint family, but has not been investigated in epithelial ovarian cancer (EOC). This study aimed to determine the B7-H7 expression profile and its potential clinical significance in EOC.MethodsA tissue microarray (TMA) containing 160 ovarian cancer tissues was used in this study and 119 EOC cases were valid for analysis. B7-H7 expression was analyzed separately by multiplex immunohistochemistry (mIHC) staining in different compartment according to tissue segmentation. Correlations of B7-H7 expression and pathological characteristics, including overall survival (OS) and disease-free survival (DFS), were explored.ResultsMultiplex immunohistochemistry staining showed that B7-H7 was broadly expressed in EOC. B7-H7 expression was significantly higher in the tumor compartment than in stromal compartment of EOC. In EOC tissues, B7-H7 expression in tumor compartment was significantly associated with age (P<0.05); B7-H7 expression in stromal compartment was significantly associated with Federation of Obstetrics and Gynecology (FIGO) stage, lymph nodes metastasis, distant metastasis, and OS (all, P<0.05). The Kaplan-Meier survival analysis revealed that high B7-H7 expression in stromal compartment was significantly correlated with the poor OS of EOC patients (P<0.05), but B7-H7 expression in tumor compartment was not.ConclusionsStromal B7-H7 expression is significantly associated with tumor progression and prognosis in EOC patients, which might be a prognostic predictor and a potential therapeutic target.

MicroRNA Expression Profiling of Epithelial Ovarian Cancer Identifies New Markers of Tumor Subtype.

Epithelial Ovarian Cancer (EOC) is often challenging to diagnose, even though histological examination. MicroRNA (miRNA or miRNA) is bound to the target messenger RNA (mRNA) due to which the mRNA molecules are silenced. The identification of miRNA expression- based EOC subtypes is considered a critical means of prognostication. So far, the studies on EOC subtypes have not been well characterized. This study aimed to confirm the existence of miRNAs in EOC and to assess their potential as clinical biomarkers for EOC. We sampled 25 ovarian tumor tissues from patients with human ovarian tumors (17 malignant; 12 serous EOC, five non-serous EOC, and eight benign ovarian tumors). miRNA microarray detection was performed to identify EOC miRNAs. Real-time PCR was adapted for the validation of differentially expressed miRNAs detected by microarray analysis related to hybridization intensity. The results confirmed that miRNAs exist in EOC, relative expression of EOC miRNAs demonstrated that the upregulation of miR-483-5p, and downregulation of miR-127-3p, and miR- 532-5p were significantly expressed in the malignant group than in the benign group at p < 0.05. Besides, miR-483-5p could also distinguish EOC subtypes between serous EOC and non-serous EOC, with a p < 0.05. A comprehensive miRNA expression profiling can help to refine subtype classification in EOC, opening new opportunities for identifying clinically applicable markers for improved stratification and diagnostics of ovarian tumors.

Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer

BackgroundOvarian cancer (OC) is a leading cause of cancer-related death in women, and thus an accurate diagnosis of the predisposition and its early detection is necessary. The aims of this study were to determine whether serum exosomal microRNA-34a (miR-34a) in ovarian cancer could be used as a potential biomarker.MethodsExosomes from OC patients’ serum were collected, and exosomal miRNAs were extracted. The relative expression of miR-34a was calculated from 58 OC samples by quantitative real-time polymerase chain reaction.ResultsSerum exosomal miR-34a levels were significantly increased in early-stage OC patients compared with advanced-stage patients. Its levels were significantly lower in patients with lymph node metastasis than in those with no lymph node metastasis. Furthermore, its levels in the recurrence group were significantly lower than those in the recurrence-free group.ConclusionsSerum exosomal miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC.

Electrochemical immunomagnetic assay as biosensing strategy for determination of ovarian cancer antigen HE4 in human serum

Prompt cancer diagnosis and treatment represent fundamental aspects to significantly improve patient survival rate. Human epididymis protein 4 (HE4) has recently been identified as promising single serum biomarker of epithelial ovarian cancer with improved diagnostic performances respect to current reference biomarkers. In this study we present the first competitive immunosensing strategy for HE4 determination implemented on magnetic microbeads functionalized with HE4 antigen. A full factorial design and multiple linear regression allowed to find the optimal experimental conditions providing the maximum inhibition rate within the explored domain. Method validation was performed in serum to ensure reliable data to support decision in clinical practice. This method allowed matching the clinically relevant concentration values for the serum biomarker, limits of detection and quantification being 2.8 and 23.0 pM, respectively. Also recovery rate in the 89 ± 7–103 ± 5% range resulted suitable for method applicability for diagnostic purposes.

Exploratory Analysis of CA125-MGL and -STn Glycoforms in the Differential Diagnostics of Pelvic Masses.

The cancer antigen 125 (CA125) immunoassay (IA) does not distinguish epithelial ovarian cancer (EOC) from benign disease with the sensitivity needed in clinical practice. In recent studies, glycoforms of CA125 have shown potential as biomarkers in EOC. Here, we assessed the diagnostic abilities of two recently developed CA125 glycoform assays for patients with a pelvic mass. Detailed analysis was further conducted for postmenopausal patients with marginally elevated conventionally measured CA125 levels, as this subgroup presents a diagnostic challenge in the clinical setting. Our study population contained 549 patients diagnosed with EOC, benign ovarian tumors, and endometriosis. Of these, 288 patients were postmenopausal, and 98 of them presented with marginally elevated serum levels of conventionally measured CA125 at diagnosis. Preoperative serum levels of conventionally measured CA125 and its glycoforms (CA125-MGL and CA125-STn) were determined. The CA125-STn assay identified EOC significantly better than the conventional CA125-IA in postmenopausal patients (85% vs. 74% sensitivity at a fixed specificity of 90%, P = 0.0009). Further, both glycoform assays had superior AUCs compared to the conventional CA125-IA in postmenopausal patients with marginally elevated CA125. Importantly, the glycoform assays reduced the false positive rate of the conventional CA125-IA. The results indicate that the CA125 glycoform assays markedly improve the performance of the conventional CA125-IA in the differential diagnosis of pelvic masses. This result is especially valuable when CA125 is marginally elevated.

Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma

Epithelial ovarian cancer (EOC) is a leading cause of cancer-related mortality in the United States due to the late-stage disease at diagnosis. Overexpression of GRP78 and PDI following endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) promote growth and invasion in cancer. To identify novel prognostic biomarkers in EOC, here we determined the expression of ER stress-associated proteins (GRP78, ATF6 and PERK) and correlated with clinical outcome in EOC. Tissue microarray (TMA) samples from 415 tissues collected from three cancer centers (UM, USC, and KCCRI) were used to assess the expression levels of ER-associated proteins using immunohistochemistry (IHC). We observed that the expression levels of GRP78 (p < 0.0001), ATF6 (p < 0.0001), and PERK (p < 0.0001) were significantly increased in specimens of EOC compared to normal tissues, including in the serous subtype (p < 0.0001). Previously we reported that high expression of PDI correlated with poor patient survival in EOC. Here we showed that overexpression of GRP78 and PDI protein expression correlated with poor patient survival (p = 0.03), while low expression of combined GRP78 and PDI correlated with better survival (p = 0.01) in high-grade serous. The increased expression of ER stress-associated proteins in EOC suggests a role for ER stress and the UPR in EOC. More importantly, our results demonstrate that GRP78 and PDI are potential biomarkers for EOC and could be used as dual prognostic markers.

High Expression of RING Finger Protein 126 Predicts Unfavorable Prognosis of Epithelial Ovarian Cancer.

BackgroundOvarian cancer (OC) is one of the leading causes of cancer-related mortality worldwide. The clinical outcome of EOC remains unsatisfactory with current therapeutic approaches such as surgery and platinum/taxane-based chemotherapy. Therefore, novel prognostic markers and personalized therapies targeting specific molecules are urgently needed. Here, we explored whether RNF126, an E3 ubiquitin ligase, is a potential biomarker for epithelial ovarian cancer (EOC).Material/MethodsThis was a retrospective cohort study of 122 EOC patients. The chi-square test was used to assess correlations between RNF126 level and clinical characteristics of enrolled patients. Univariate and multivariate analyses were performed to monitor the prognosis of enrolled patients. In addition, proliferation and invasion assays were conducted to assess the cellular effects of RNF126 on SKOV3 cell progression.ResultsImmunohistochemistry analysis (IHC) revealed that RNF126 was upregulated in EOC tissues compared to adjacent ovarian tissues. In addition, RNF126 expression was remarkably associated with LN metastasis, pathological differentiation, and FIGO stage. RNF126 protein level was found to be an independent biomarker for predication of prognosis in ovarian cancer patients. Cellular results showed that RNF126 enhanced the proliferation and invasion abilities of SKOV3 cells.ConclusionsUpregulated protein level of RNF126 in EOC tissues is a biomarker predicting poor outcomes of EOC patients.

Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells.

ObjectiveEarly detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC.MethodsQuantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed.ResultsCirculating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p.ConclusionscircFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.

Clinical significance of microRNA-125b and its contribution to ovarian carcinogenesis

ABSTRACT The underlying mechanisms of recurrence and metastasis of epithelial ovarian cancer (EOC) are largely unknown. In the present study, we investigated the clinical significance of microRNA-125b (miR-125b) and its role in ovarian tumorigenesis and progression. Seventy patients of EOC and paired tissues were enrolled from 2015 to 2017. qRT-PCR was used to evaluate miR-125b expression in tumor tissues and EOC cell line. Gain-and-loss function of miR-125b was achieved to explore the changes in cell biological function. We found that miR-125b expression in EOC tissues, especially in the high-grade tissues (P < 0.001), was significantly lower compared to the matched adjacent noncancerous tissues and associated with pathological type, stage, and overall survival (P < 0.05). Upregulation of miR-125b promoted apoptosis and decreased cell survival rate and migration, and vice versa in vitro. Mechanistically, miR-125b negatively regulated S100A4, a metastasis-associated protein. MiR-125b overexpression significantly decreased tumor growth and inhibited lung metastasis in vivo. Our results supported that miR-125b contributes to the progression of EOC by targeting S100A4. It potentially acts as a potential biomarker and therapeutic target of EOC.