Prognosis Of Epithelial Ovarian Cancer Research Articles

Long Noncoding RNA SNHG15 Serves as an Oncogene and Predicts Poor Prognosis in Epithelial Ovarian Cancer [Expression of Concern

Long Noncoding RNA SNHG15 Serves as an Oncogene and Predicts Poor Prognosis in Epithelial Ovarian Cancer [Expression of Concern

The Combination of Plasma Fibrinogen Concentration and Neutrophil Lymphocyte Ratio (F-NLR) as a Prognostic Factor of Epithelial Ovarian Cancer.

ObjectiveGrowing epidemiological evidence supports that coagulation cascades and cancer-associated inflammation are associated with recurrence and survival of epithelial ovarian cancer (EOC). This study aimed to assess the clinical significance of the combination of plasm fibrinogen and neutrophil lymphocyte ratio (F-NLR) score to predict EOC prognosis, including recurrence, disease-free survival (DFS), and overall survival (OS).Patients and MethodsWe retrospectively enrolled 281 EOC patients who underwent surgery at our institution. According to receiver operating characteristic curve, cut-off values of fibrinogen and NLR were set at 3.44 g/L and 2.46, respectively, to predict recurrence. The F-NLR score was then classified into three groups as follows: F-NLR score of 2: both hyperfibrinogenemia (>3.44 mg/dL) and high NLR (>2.46), F-NLR score of 1: either hyperfibrinogenemia or high NLR, and F-NLR score of 0: neither of the abnormalities. Continuous and categorical variables were compared using T-test and chi-square test among F-NLR groups. The Cox hazard regression model was used to assess prognostic factors. Both DFS and OS curves were generated by Kaplan–Meier method.ResultsThe analyses showed that F-NLR was significantly associated with clinical stage (P=0.000), lymphatic metastasis (P=0.001), and carbohydrate antigen (CA) 125 level (P=0.048). The F-NLR (hazard ratio=2.211; 95% confidence interval=1.251–6.394; P=0.002) was demonstrated as an independent prognostic factor for survival of EOC. The DFS rates in F-NLR groups 0, 1, and 2 were 68.5%, 47.7%, and 31.7%, respectively (P=0.000); the OS rates in previous groups were 75.9%, 51.4%, and 34.2% (P=0.000) and the 5-year survival times (mean±SD, months) were 64.24±24.21, 60.27±22.65, and 46.09±20.32, respectively. By subgroup analysis, the F-NLR was significantly associated with DFS and OS among patients with advanced tumor stage (Stage III or IV) or lymphatic metastasis.ConclusionThe pre-operative F-NLR score, a novel inflammation-based grading system, was a promising prognosis predictor for EOC patients, especially those with advanced clinical stage and those with lymph node metastasis.

Differential Expression Pattern of Epithelial Mesenchymal Transition Gens; AXL, GAS6, Claudin-1, and Cofilin-1, in Different Stages of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC), is the fatal form of gynecological cancer. Almost 70% of ovarian cancer patients are detected at an advanced stage (III-IV) with metastases. Epithelial-mesenchymal transition (EMT) is a critical process associated with metastasis. This study investigated the expression levels of AXL, GAS6, Claudin-1, and Cofilin-1, as genes involved in EMT in relation to clinicopathologic features in ovarian cancer patients. In this descriptive study, 78 ovarian epithelial cancer patients were enrolled. Samples were provided by the Iran National Tumor Bank, founded by the Cancer Institute of Tehran University of Medical Sciences in 2017. The expression levels of AXL, GAS6, Claudin-1, and Cofilin-1 genes were investigated in a fresh, frozen tumor sample and normal adjacent tissue by real-time PCR (RT-PCR). Findings showed a significant relationship between the overexpression of AXL and TNM staging (P=0.03). The expression level of GAS6 decreased in more advanced stages (P=0.01). There is a negative relationship between Cofilin-1 expression level and TNM staging (P=0.002). Claudin-1 expression level was higher in low stages compared with that in high stages (P=0.01). There was no relationship between gene expression levels of target genes with size and grade of the tumor. Given the importance of these genes in EMT, alteration in their expression pattern can contribute to the progression of the disease and distant metastasis of cancer cells. Additionally, knowing the alteration pattern of these genes expression can help to better understanding and prediction of the prognosis of EOC.

PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer.

IntroductionA growing number of studies have found that the serine-glycine biosynthesis pathway is highly activated for biosynthesis in cancer progression and metastasis. Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step of the serine-glycine biosynthesis pathway; the effects and mechanism of PSAT1 in epithelial ovarian cancer (EOC) remains unclear.Materials and MethodsThe expression of PSAT1 in clinical EOC samples and normal ovarian tissues was conducted by RT-PCR, Western blot, and immunohistochemical staining. Survival analysis of PSAT1 in ovarian cancer was performed by using the public database. Following the downregulation of PSAT1, the cell growth, cell apoptosis, and cell cycle in ovarian cancer cells were respectively examined by the soft agar colony formation assay and flow cytometry analysis. Then the glutathione (GSH) levels, the GSH/GSSG ratio, the NADPH/NADP ratio, and the cellular reactive oxygen species (ROS) levels were tested to analyze the oxidation-reduction balance in PSAT1-depleted ovarian cancer cells.ResultsPSAT1 is markedly over-expressed in clinical EOC samples (n = 90) compared to that in normal ovarian tissues (n = 10), and the expression of PSAT1 is correlated with histological subtype, FIGO stage, histological grade, lymph node metastasis, distant metastasis and the presence of ascites. Public database analysis shows that higher PSAT1 indicates poor survival in EOC patients. Downregulation of PSAT1 in EOC cells inhibits growth, induces apoptosis and cell cycle arrest in vitro. EOC cells with high PSAT1 levels have increased a higher GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio and lower reactive oxygen species (ROS) content. The cancer-killing effects of PSAT1 knockdown are reversed by exogenous glutathione. PSAT1 participates in cancer growth by regulating oxidation-reduction balance.ConclusionTherefore, these results highlight the potential of PSAT1 inhibitors or metabolic substrate deprivation as therapeutic strategies for treating patients with EOC, especially those with advanced stages of cancer.

Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer

BackgroundThe mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin–dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients.MethodsExpression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0–12. The expression scores calculated were correlated with clinicopathological parameters and patient survival.ResultsHigh immunoreactivity of phospho-Drp1Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (p = 0.006), and non-responders to adjuvant chemotherapy (p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p = 0.011) and platinum-resistant recurrence (p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1Ser637 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039–9.561].ConclusionsDrp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.

OvarianTag biomarker panel in order guide treatment decisions cisplatin-based for women with epithelial ovarian cancer.

e18075 Background: Ovarian cancer (OC) represents the most lethal gynecologic cancer. Late-stage diagnosis associated with a lack of effective markers to detect chemotherapy resistance contributes to high mortality and poor prognosis of epithelial ovarian cancer (EOC). OvarianTag Biomarkers Panel was developed as biopsy-based gene expression assay to discriminate prognosis in EOC patients, to understand the aggressiveness and relapse causes of these patients. Methods: Patients were admitted into this study in two phases. First, 45 women were included prospectively, and RNA was obtained from fresh normal ovarian (NO) tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and EOC (n = 16). The total RNA content was quantified and quantitative PCR (qRT-PCR) was performed to determine relative gene expression, starting set genes related to apoptosis and necroptosis regulated cell death pathway. Machine Learning algorithms were used to classify patient’s data associated and to characterize molecular targets as prognostic markers, named OvarianTag panel. Later, others 55 EOC patients, attended between 2008 and 2016, were included. Within this cohort, tissues were obtained from 106 FFPE samples and shared into primary and metastatic EOC, and from the same NO tissues (as control). RNA was extracted and qRT-PCR determined the OvarianTag panel expression level from each sample. Then, hierarchical clustering allowed us to classify the samples using the cut off obtained by classifier algorithm. Results: Significant differences in gene expression profile were observed between patients’ groups. Molecular classifier algorithm proved the prognostic value of genes evaluated. Decisions trees and biomarker clusters were constructed. In the full training, were obtained 90% of correct classifications and in cross-validation, 89%. In the second phase, the classifier reported specificity of 100% and sensibility of 79% to predict tumor recurrence and platinum resistance. Conclusions: OvarianTag panel is a putative prognosis biomarker of EOC subgroups and could be considered to drive the clinical practice of EOC treatment options, improving outcomes because providing an opportunity for guide clinical intervention for increasing survival rates. Besides of that, it will be allowed include patients in clinical trials of new target drugs or for repositioning of target drugs that have already been tested in humans.

Eukaryotic initiation factor 3B is overexpressed and correlates with larger tumor size, advanced FIGO stage, and shorter overall survival in epithelial ovarian cancer patients.

BackgroundThis study aimed to detect the eukaryotic initiation factor 3B (EIF3B) expression and explore its correlation with clinical features and prognosis in epithelial ovarian cancer (EOC) patients.Methods A total of 230 primary EOC patients underwent surgery treatment were retrospectively reviewed. Immunohistochemical (IHC) assay was used to determine EIF3B expression in tumor and adjacent tissue specimens of all patients. According to the total IHC score, the expression of EIF3B was classified as low expression and high expression, and the latter was further divided into 3 grades: high+, high++, and high+++ expressions. Overall survival (OS) was calculated.ResultsEukaryotic initiation factor 3B expression was increased in tumor tissue compared with adjacent tissue. Tumor EIF3B high expression correlated with larger tumor size (>10 cm), lymphatic metastasis, and advanced International Federation of Gynecology and Obstetrics stage (FIGO) (III/IV). Besides, OS was decreased in patients with tumor EIF3B high expression compared with patients with tumor EIF3B low expression, and further analysis showed that the OS was shortest in patients with tumor EIF3B high+++ expression, followed by patients with tumor EIF3B high++ expression and patients with tumor EIF3B high + expression, and the longest in patients with tumor EIF3B low expression. Additionally, higher tumor EIF3B expression, peritoneal cytology (positive), ascites volume (>100 mL), differentiation (poor vs. well/moderate), tumor size (>10 cm), FIGO stage (III/IV vs. I/II), and cancer antigen 125 (>1000 U/mL) independently predicted shorter OS.ConclusionEukaryotic initiation factor 3B exhibits a clinical value for monitoring disease progression and predicting prognosis in EOC patients.

ABCC4/MRP4 contributes to the aggressiveness of Myc-associated epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters are known for roles in both drug resistance and cancer biology and are also highly targetable. Here we have investigated the association of ABCC4/MRP4 expression to clinical outcome and its biological function in endometrioid and serous tumors, common histological subtypes of EOC. We found high expression of ABCC4/MRP4, previously shown to be directly regulated by c-Myc/N-Myc, was associated with poor prognosis in endometrioid EOC (P = .001) as well as in a subset of serous EOC with a "high-MYCN" profile (C5/proliferative; P = .019). Transient siRNA-mediated suppression of MRP4 in EOC cells led to reduced growth, migration and invasion, with the effects being most pronounced in endometrioid and C5-like serous cells compared to non-C5 serous EOC cells. Sustained knockdown of MRP4 also sensitized endometrioid cells to MRP4 substrate drugs. Furthermore, suppression of MRP4 decreased the growth of patient-derived EOC cells in vivo. Together, our findings provide the first evidence that MRP4 plays an important role in the biology of Myc-associated ovarian tumors and highlight this transporter as a potential therapeutic target for EOC.

FOXO1 overexpression is correlated with poor prognosis in epithelial ovarian cancer

To investigate FOXO1 expression in epithelial ovarian cancer (EOC), and to explore its correlation with clinicopathological parameters and prognosis of EOC. Two hundred and sixteen cases of paraffin-embedded EOC and 41 paratumor tissues from 2009 to 2017 that had been pathologically confirmed at the memorial hospital of Sun Yat-sen University were included in this study, and the expression of FOXO1 was performed by immunohistochemistry using a polyclonal antibody specific for FOXO1. FOXO1 protein expression is associated with Recurrence free and overall survival in EOC patients; In addition, FOXO1 expression is associated with age, FIGO stage, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence and differentiation grade; Moreover, in a multivariate model FOXO1 overexpression was an independent predictor of poor survival in EOC. FOXO1 may play a candidate oncogenic role in EOC, and FOXO1 is a useful independent prognostic marker in EOC, and it may provide a candidate target therapy in future.

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer

BackgroundLow expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis.MethodsHigh-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter.ResultsIn patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-β signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS.ConclusionsNCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.

Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes.

MiR-6089/MYH9/β-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression

The pathogenesis of ovarian cancer remains to be elucidated. Our previous study demonstrated that myosin heavy chain 9 (MYH9) overexpression was associated with poor prognosis of epithelial ovarian cancer. However, the mechanism of MYH9 and its regulation by microRNA (miR) is not clear. The results of the present study demonstrated that miR-6089 was one of the microRNAs targeting MYH9, and miR-6089 overexpression suppressed ovarian cancer cell proliferation, migration, invasion and metastasis in vivo and in vitro. Mechanistic studies confirmed that miR-6089 directly targeted MYH9 to inactivate the Wnt/β-catenin signalling pathway and its downstream epithelial-to-mesenchymal transition (EMT), cell-cycle factors and c-Jun, whereas overexpression of MYH9 reversed the inhibitory effects of miR-6089 overexpression in ovarian cancer cells by upregulating the Wnt/β-catenin and its downstream EMT, cell-cycle factors and c-Jun. Interestingly, miR-6089 was transcriptionally inhibited by c-Jun, a transcription factor which could be induced by MYH9 via the Wnt/β-catenin pathway. Thus miR-6089/MYH9/β-catenin/c-Jun formed a negative feedback loop in ovarian cancer. In clinical samples, miR-6089 negatively correlated with MYH9 expression. Our study is the first to demonstrate that miR-6089 serves as a tumor-suppressive miRNA, and miR-6089/MYH9/β-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression.

C-C motif chemokine 14 as a novel potential biomarker for predicting the prognosis of epithelial ovarian cancer.

Previous studies have demonstrated that C-C motif chemokine 14 (CCL14) plays an important role in the occurrence and development of cancer. However, the significance of CCL14 in the progression and prognosis of epithelial ovarian cancer (EOC) has not yet been reported. The standard EnVision procedure for tissue microarrays was used to evaluate the immunohistochemical expression of CCL14 protein in 154 patients with EOC who underwent tumor-debulking operations at the Central Cancer Department of Sun Yat-Sen University (Guangzhou, China) or Jiangmen Central Hospital (Jiangmen, China). The association between CCL14 expression and clinicopathological variables was assessed using the χ2 test. For survival status of patients with EOC, Kaplan-Meier survival analysis and a Cox multivariate regression model was used. Expression of CCL14 protein was significantly associated with International Federation of Gynecology and Obstetric stage (P=0.014) and pN status(P=0.005). Kaplan-Meier survival analysis revealed that the survival time of patients with high expression of CCL14 was 136.1 months and that of patients with low expression of CCL14 was 98.9 months (P=0.026). Multivariate analysis demonstrated that CCL14 upregulation was associated with overall survival time (HR, 0.48; 95% CI, 0.261–0.896; P=0.021) and progression-free survival time (HR,0.437; 95% CI, 0.228–0.839; P=0.013). In conclusion, CCL14 is an independent prognostic factor for EOC and upregulation of CCL14 is associated with a more favorable prognosis in patients with EOC.

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.

Histological Tumor Type is Associated with One-Year Cause-Specific Survival in Women with Stage III-IV Epithelial Ovarian Cancer: A Surveillance, Epidemiology, and End Results (SEER) Database Population Study, 2004-2014.

BackgroundThe prognosis of epithelial ovarian cancer (EOC) remains poor. Cause-specific survival (CSS) is an overall survival measure of cancer survival that excludes other causes of death. This retrospective population study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors associated with one-year CSS in women with stage III–IV EOC between 2004–2014.Material/MethodsData from the SEER program included a cohort of patients with stage III–IV EOC between 2004–2014. Binomial logistic regression analysis, Kaplan-Meier survival curves, and multivariate Cox proportional hazards models were used for analysis of patient outcome, including the one-year CSS.ResultsThere were 14,798 patients with stage III–IV EOC identified from SEER between 2004–2014, including 13,134 (88.8%), 892 (6.0%), 448 (3.0%), and 324 (2.2%) patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively. The overall one-year CSS was 91.2%. One-year CSS was 92.5%, 92.2%, 74.0%, and 62.5% in patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively (P<0.001). Histological tumor type was an independent prognostic factor of one-year CSS. Patients with mucinous EOC (HR, 8.807; 95% CI, 6.563–9.965; P<0.001) and clear cell EOC (HR, 4.581; 95% CI, 3.774–5.560; P<0.001) had a significantly lower one-year CSS compared with patients with endometrioid and serous EOC who had comparable one-year CSS (HR, 1.247; 95% CI, 0.978–1.590; P=0.075).ConclusionsA retrospective population study of the SEER database between 2004–2014 identified that histological tumor type was associated with one-year CSS in women with stage III–IV EOC.

BRCA1 Expression by Immunohistochemistry and Prognosis in Ovarian Cancer: A Systematic Review and Meta-Analysis.

Homologous recombination deficiencies are associated with increased platinum sensitivity and potential response to poly (ADP-ribose) polymerase inhibitors in epithelial ovarian cancer. As an alternative to germline testing or somatic tumor sequencing, BRCA1 deficiency can be detected by immunohistochemistry and might predict homologous recombination deficiencies. This study aimed to assess the association between BRCA1 expression by immunohistochemistry and the prognosis of patients with epithelial ovarian cancer. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We searched PubMed, EMBASE, Web of Science, and Scopus databases through July 2019. Reference lists of selected articles were screened for further studies. We conducted qualitative synthesis and meta-analyses of hazard ratios for overall survival and progression-free survival. Of 41 studies of BRCA1 expression using immunohistochemistry, 18 evaluated the association of BRCA1 expression with patient survival (2738 cases). The loss of BRCA1 expression was associated with improved overall survival (hazard ratio = 0.67, 95% confidence interval 0.57-0.77) and progression-free survival (hazard ratio = 0.70, 95% confidence interval 0.58-0.84). Negative BRCA1 expression assessed by immunohistochemistry was associated with a better prognosis in epithelial ovarian cancer.

Prognostic factors for types I and II epithelial ovarian cancer in the elderly

Purpose: No consensus exists on whether age is independently associated with poor prognosis in epithelial ovarian cancer (EOC). This study aimed to examine the prognostic factors of EOC in elderly patients. Materials and Methods:A total of 665 EOC patients from Jiangsu Institute of Cancer Research (JICR, People’s Republic of China) were retrospectively analyzed between 1996 and 2015. For validation, 990 cases who consulted at MD Anderson Cancer Center (MDACC, USA) from 1990 to 2011 were recruited. The associations between survival durations and covariates were assessed by Cox proportional hazards model and log-rank test. Results: Histological type II (p = 0.01) and suboptimal surgery outcome (p = 0.00) were more common in the elderly (age ≥ 70 years) patients with EOC than in younger patients from JICR. The International Federation of Gynecology and Obstetrics (FIGO) stage, histological type, and optimal surgery were independently associated with overall survival (OS; p = 0.00, p = 0.03, and p = 0.00, respectively) and progression-free survival (PFS; p = 0.00, p = 0.02, and p = 0.00, respectively) in the EOC patients. Both OS and PFS were lower in the elderly patients with type I EOC than in the younger cases (136.5 months vs. 191.8 months at p = 0.00 and 35.5 months vs. 75.1 months at p = 0.01, respectively). The OS and PFS of the elderly patients were poorer than those of the younger cases with type II EOC (38.4 months vs. 42.3 months at p = 0.00 and 14.9 months vs. 16.8 months, p = 0.04, respectively). In type II ovarian cancer patients who achieved optimal debulking, the median OS and PFS durations of younger patients remained longer than those of elderly patients (50.2 months vs. 68.0 months, p = 0.00 and 14.9 months vs. 19.2 months, p = 0.01, respectively). Conclusions: Compared with young patients, elderly EOC more commonly presented with an aggressive histological type and poor performance status and was more frequently undertreated. Advanced age was independently associated with poor prognosis in EOC, even after the influence of histological type and surgical outcome was eliminated.

The clinical value of the combined detection of sEGFR, CA125 and HE4 for epithelial ovarian cancer diagnosis.

This study aims to investigate the clinical value of combined detection of serum soluble epidermal growth factor receptor (sEGFR), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in the diagnosis of epithelial ovarian cancer (EOC). From December 2017 to October 2018, the serum samples were obtained from the Affiliated Hospital of Xuzhou Medical University, with 30 patients as EOC group, 30 patients with benign ovarian neoplasms as benign group, and 17 healthy subjects as healthy group. Besides, among 30 EOC patients, 9 serum samples were obtained from pre-operative and post-operative EOC patients. The levels of serum sEGFR were detected by enzyme-linked immunosorbent assay (ELISA), while CA125 and HE4 were detected by enhanced chemiluminescence immunoassay (ECLIA). The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. The levels of serum sEGFR, CA125, and HE4 in EOC group were significantly higher than those in benign group (p<0.05) and healthy group (p<0.05). When using a single tumor marker, the CA125 shows the highest sensitivity (93.30%) and HE4 shows the highest specificity (97.87%). The specificity of combined detection of serum sEGFR, CA125, and HE4 was 100%, which was significantly higher than that using a single tumor marker. The area under the ROC curve (AUC) of combined detection of serum sEGFR, CA125, and HE4 (0.965) was much higher than that of the single detection and higher than that of combined detection of CA125 and HE4 (0.940). Moreover, the level of serum sEGFR in post-operative EOC group was significantly lower than that in the corresponding pre-operative EOC group (p<0.05). Our study shows that combined detection of serum sEGFR, CA125, and HE4 increases the specificity and efficiency in EOC diagnosis, indicating that sEGFR could be a potential biomarker for the diagnosis and prognosis of EOC.

Multi-omics analysis of tumor mutational burden combined with prognostic assessment in epithelial ovarian cancer based on TCGA database.

Background: Tumor mutation burden (TMB) is considered as a novel biomarker of response to immunotherapy and correlated with survival outcomes in various malignancies. Here, TMB-related genes (TRGs) expression signatures were constructed to investigate the association between TMB and prognosis in epithelial ovarian cancer (EOC), and the potential mechanism in immunoregulation was also explored.Methods: Based on somatic mutation data of 436 EOC samples from The Cancer Genome Atlas database, we examined the relationship between TMB level and overall survival (OS), as well as disease-free survival (DFS). Next, the TRGs signatures were constructed and validated. Differential abundance of immune cell infiltration, expression levels of immunomodulators and functional enrichment in high- and low-risk groups were also analyzed.Results: Higher TMB level revealed better OS and DFS, and correlated with earlier clinical stages in EOCs (P = 2.796e-04). The OS-related prognostic model constructed based on seven TRGs (B3GALT1, LIN7B, ANGPT2, D2HGDH, TAF13, PFDN4 and DNAJC19) significantly stratified EOC patients into high- and low-risk groups (P < 0.001). The AUC values of the seven-gene prognostic signature at 1 year, 3 years, and 5 years were 0.703, 0.758 and 0.777. While the DFS-related prognostic model was constructed based on the 4 TRGs (LPIN3, PXYLP1, IGSF23 and B3GALT1), with AUCs of 0.617, 0.756, and 0.731, respectively. Functional analysis indicated that immune‐related pathways were enriched in low‐risk groups. When considering the infiltration patterns of immune cells, we found higher proportions of follicular helper T (Tfh) cell and M1 macrophage, while lower infiltration of M0 macrophage in low-risk groups (P < 0.05). Accordingly, TMB levels of low-risk patients were significantly higher both in OS and DFS model (P < 0.01).Conclusions: Our TRGs-based models are reliable predictive tools for OS and DFS. High TMB may confer with an immunogenic microenvironment and predict favorable outcomes in EOCs.

Low expression of KIF7 indicates poor prognosis in epithelial ovarian cancer.

The aim of the present study was to investigate kinesin family member 7 (KIF7) expression in epithelial ovarian cancer tissues (paraffin-embedded tissues and fresh) and to explore its expression, association with clinicopathological parameters and prognostic value in patients with epithelial ovarian cancer. A total of 113 paraffin-embedded tumor tissues of epithelial ovarian cancer patients diagnosed and operated at the memorial hospital of Sun Yat-sen University Between December 2009 and March 2017 and 41 paratumor tissues were collected for the present study and were assessed for KIF7 expression using immunohistochemistry. Furthermore, 22 fresh epithelial ovarian cancer tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and March 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of KIF7. The expression of KIF7 was lower in cancer tissues than in paratumor tissues, and KIF7 expression was associated with recurrence-free survival and overall survival in epithelial ovarian cancer patients. Furthermore, multivariate logistic regression analysis indicated that low KIF7 expression was an independent predictor of poor survival in patients with epithelial ovarian cancer. In conclusion, KIF7 has a tumor suppressor role in epithelial ovarian cancer and is a useful independent prognostic predictor. It may hold important value for the clinical diagnosis and treatment of epithelial ovarian cancer.