Factor In Epithelial Ovarian Cancer Research Articles

Optimal cutoff age for predicting prognosis associated with serous epithelial ovarian cancer: what is the best age cutoff?

ObjectiveElderly age is one of the poor prognostic factors in epithelial ovarian cancer (EOC), but the optimal age cut-off is not known. The present study sought to identify the ideal age cutoff that represents a negative prognostic factor in EOC, considering the geriatric assessment.MethodsHazard ratios (HRs) with p-values were calculated using all possible age cutoffs with stage, histology, grade, optimality and comorbidities as covariates in multivariate Cox regression model. The trends of p-value and HR by age cutoff were further evaluated in a subgroup of histology and in The Cancer Genome Atlas (TCGA) dataset. In addition, propensity score-matching analysis using the identified age cutoff was performed.ResultsAn age of 66 years was shown to be the most significant cutoff for defining old age with independent prognostic power (HR=1.45; 95% confidence interval=1.04–2.03; p=0.027). This result was also observed with the analyses of serous histology subgroup and with the analysis of a TCGA dataset with serous EOC. In survival analysis, patients aged ≥66 years had significantly worse overall survival compared with younger individuals (56 months vs. 87 months; p=0.006), even following propensity score matching (57 vs. 78 months; p=0.038).ConclusionAn age of 66 years is the best cutoff to define elderly age in serous EOC patients considering the geriatric assessment, and this information can be used in the administration of individualized therapies in elderly EOC patients.

Clinico-Epidemiological Study of Epithelial Ovarian Cancer Mansoura Experience

Background & objective: Ovarian cancer is the fifth most common cancer affecting women today. The aim of this retrospective study was to present the epidemiological, pathological, clinical characteristics of epithelial ovarian cancer patients treated at Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospitals in the period between January 2009 and December 2013, with evaluation of progression free survival (PFS) overall survival (OS) and prognostic factors. Patients & methods: This is a retrospective study of epithelial ovarian carcinoma women treated at Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospitals (in the period between January 2009 and December 2013). Data were analyzed after being collected from the patients' medical records. Clinical abstract sheets for all cases were designed. Results: The median age was 55 years (19 – 80 years), 58 patients (39.2%) were ECOG performance status (PS) 1, whereas, 50 patients (33.8%) were PS 0 at presentation. Ninety five patients (64.2%) were postmenopausal at presentation, serous cystadenocarcinoma was the predominant histopathologic type found in 94 patients (63.5%), followed by Endometrioid type (17.5%), 79 patients (53.4%) had stage III disease and 33 patients (22.3%) had stage IV disease. The majority of patients (99 patients 66.9%) had grade III tumors, 140 patients (94.6%) in the study underwent surgical treatment, optimal debulking was done in 85 patients (60.7%), while, suboptimal debulking was done in 55 patients (39.3%), the median overall survival was 49 months, while the median progression free survival was 18 months. Conclusion: the median age was 55 years old, serous carcinoma was the predominant histopathological type. Stage III and IV predominated. Most patients underwent initially surgery followed by adjuvant chemotherapy. The median overall survival & PFS were 49 & 18 months, respectively. Age, tumor histopathology, stage, grade and tumor residue after debulking surgery were significant independent prognostic factors for epithelial ovarian cancer.

Increased expression of long noncoding RNA HMMR-AS1 in epithelial ovarian cancer: an independent prognostic factor.

Evidence has indicated that long noncoding RNA (lncRNAs) may have significant roles in cancer. In this study, we aimed to investigate the expression pattern and prognostic value of a noncoding RNA named as HMMR antisense RNA 1 (HMMR-AS1) in epithelial ovarian cancer (EOC). Differences in the expression of HMMR-AS1 between EOC and matched normal tissues were analyzed using RT-PCR. The correlation between HMMR-AS1 levels and the clinicopathological factors of the EOC patients was analyzed by x2-test. Kaplan-Meier analysis and Cox proportional hazards regression models were explored to reveal the correlations of HMMR-AS1 expression with survival of patients. HMMR-AS1 was significantly upregulated in human EOC tissues compared with adjacent normal tissues (p < 0.01). Clinicopathologic analysis revealed that high expression of HMMR-AS1 was associated with advanced FIGO stage (p = 0.013) and positive lymphatic metastasis (p = 0.010). Moreover, patients with higher HMMR-AS1 expression displayed shorter overall survival time (p = 0.0075) and progression-free survival time (p = 0.0013) than those with lower HMMR-AS1 expression. More importantly, multivariate analysis suggested that high expression of HMMR-AS1 was an independent prognostic indicator for EOC patients. Our data suggested that HMMR-AS1 may be considered a novel prognostic factor in EOC and a specific diagnostic indicator for patients with EOC.

Impact of the new FIGO 2013 classification on prognosis of stage I epithelial ovarian cancers.

PurposeThe stage of disease is one of the strongest prognostic factors in epithelial ovarian cancer. The International Federation of Gynecology and Obstetrics (FIGO) classification was revised in 2013; stage IC was subdivided into IC1 (intraoperative surgical spill), IC2 (capsule rupture before surgery or tumor on surface), and IC3 (positive peritoneal washing or ascites). Our aim was to compare the outcome of patients in the new FIGO stage I subgroups, as this might influence adjuvant therapy decisions.Patients and methodsPatient databases of three gynecological oncology centers were retrospectively analyzed. Patients with FIGO stage I ovarian cancers were restaged according to the revised classification, based on operative and pathological reports, and determined patient outcomes.ResultsWe analyzed 128 patients with ovarian cancers. In FIGO IA, we found 11.3% recurrences and 4.2% deaths. In FIGO IC, 21.8% of the patients recurred and 7.3% died. There was a trend toward a shorter time to recurrence when comparing IA to IC (P=0.076). Within all new subgroups of FIGO IC, there was no difference in time to recurrence (P=0.59). There was also no significant difference in survival when FIGO IA was compared to FIGO IC in comparison with the new individual classifications (IA to IC, IA to IC1, 2, or 3; P=0.60, P=0.15, P=0.61, P=0.66, respectively) or within the different subgroups (P=0.56). Platinum-based chemotherapy was given to the majority (82.6%, n=38/46) of the FIGO IC patients compared to 30.9% in FIGO IA (n=17/55). There was no significant difference within the new subgroups of FIGO IC (P=0.88).ConclusionIn our retrospective analysis, the new FIGO staging of IC ovarian cancers did not predict prognosis, but the use of adjuvant chemotherapy in 82.6% of the stage IC patients may have biased the outcome.

A predictive score for optimal cytoreduction at interval debulking surgery in epithelial ovarian cancer: a two- centers experience

BackgroundOptimal cytoreduction (macroscopic Residual Tumor, RT = 0) is the best survival predictor factor in epithelial ovarian cancer (EOC). It doesn’t exist a consolidated criteria to predict optimal surgical resection at interval debulking surgery (IDS). The aim of this study is to develop a predictive model of complete cytoreduction at IDS.MethodsWe, retrospectively, analyzed 93 out of 432 patients, with advanced EOC, underwent neoadjuvant chemotherapy (NACT) and IDS from January 2010 to December 2016 in two referral cancer centers. The correlation between clinical-pathological variables and residual disease at IDS has been investigated with univariate and multivariate analysis. A predictive score of cytoreduction (PSC) has been created by combining all significant variables. The performance of each single variable and PSC has been reported and the correlation of all significant variables with progression free survival (PFS) has been assessed.ResultsAt IDS, 65 patients (69,8%) had complete cytoreduction with no residual disease (R = 0). Three criteria independently predicted R > 0: age ≥ 60 years (p = 0.014), CA-125 before NACT > 550 UI/dl (p = 0.044), and Peritoneal Cancer Index (PCI) > 16 (p < 0.001). A PSC ≥ 3 has been associated with a better accuracy (85,8%), limiting the number of incomplete surgeries to 16,5%. Moreover, a PCI > 16, a PSC ≥ 3 and the presence of R > 0 after IDS were all significantly associated with shorter PFS (p < 0.001, p < 0.001 and p = 0.004 respectively).ConclusionsOur PSC predicts, in a large number of patients, complete cytoreduction at IDS, limiting the rate of futile extensive surgeries in case of presence of residual tumor (R > 0). The PSC should be prospectively validated in a larger series of EOC patients undergoing NACT-IDS.

TNF-R2 in tumor microenvironment as prognostic factor in epithelial ovarian cancer.

The aims of the study were to compare the levels of tumor necrosis factor alpha (TNF-α) and its soluble type I (sTNF-R1) and type II (sTNF-R2) receptors detected in intracystic liquid and serum from benign and malignant ovarian neoplasms and to relate them to prognostic factors in epithelial ovarian cancer. The patients were divided into benign ovarian neoplasms (n = 46) and malignant ovarian neoplasms (n = 17). The serum and intracystic samples were collected before and during surgery for ovarian cyst, respectively. The levels of TNF-α, sTNF-R1, and sTNF-R2 were measured using ELISA. Results were compared with the Mann-Whitney test. Concentration of sTNF-R2 in the intracystic samples collected from the malignant neoplasia was significantly higher than that of the benign neoplasias (p = 0.02). Higher intracystic levels of sTNF-R2 exhibited a significant association with tumor differentiation grades 2 and 3 (p = 0.0087). There was no statistical significance in relation to serum levels. Tumor microenvironment levels of sTNF-R2 may represent a factor of poor prognosis in epithelial ovarian cancer.

Prognostic factors in epithelial ovarian cancer: A population-based study.

The overall survival (OS) of patients with ovarian cancer is poor while epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of the present study was to evaluate the clinico-pathologic characteristics, especially the prognostic factors, for patients with epithelial ovarian cancer (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to 2012 was retrieved from the database of the Taiwan Cancer Registry. Data from 2009 to 2013 for the respective cases from the claims database of Taiwan’s National Health Insurance and National Death Registry were then retrieved. Potential prognostic factors were analyzed. The mean age at diagnosis of the 2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002, p<0.001, respectively) in multivariable analysis. For advanced-stage patients, histology (endometrioid type), taxane-based adjuvant chemotherapy, stage, and age at diagnosis had a significant impact on OS (p<0.001, p = 0.020, p<0.001, p<0.001, respectively). In conclusion, taxane-based chemotherapy impacts the outcome of patients with EOC. Personalized medicine may be needed for different histological types of EOC because of their different outcomes.

High Immune Expression of Progesterone-Induced Blocking Factor in Epithelial Ovarian Cancer.

Background:Progesterone-induced blocking factor, which is released from maternal lymphocytes during pregnancy mediates the immune effect of progesterone. According to new reports, it is suggested that proliferating cells, such as human trophoblasts, mesenchymal stem cells, and malignant tumors, can excrete progesterone-induced blocking factor at high ratio to escape from maternal immunity. It is shown in recent studies that progesterone-induced blocking factor is overexpressed in many malignant tumors such as breast, cervical, lymphoma, and leukemia. There are no data about progesterone-induced blocking factor expression in ovarian cancer cells. Hence, it is aimed to determine the progesterone-induced blocking factor expression levels in epithelial ovarian cancer.Methods:The study which was a retrospective cross-sectional study was conducted in a University Hospital. Twenty tissue specimens of patients with epithelial ovarian cancer and 20 tissue specimens of patients with healthy ovary were included in the study. Primary rabbit polyclonal anti- progesterone-induced blocking factor antibody was used to incubate the sections at a ratio of 1:300.Results:When the tissue sections were compared based on immunostaining with progesterone-induced blocking factor, we detected high stromal progesterone-induced blocking factor expression in the epithelial ovarian cancer group as check against to the normal ovarian group (P = .007). Similarly, we found high glandular progesterone-induced blocking factor expression in the epithelial ovarian cancer group as check against to the normal ovarian group (P < .001).Conclusion:Proving the existence of progesterone-induced blocking factor expression in epithelial ovarian cancer cells may lead new visions or new studies for epithelial ovarian cancer immunotherapy. As a result, epithelial ovarian cancer cells have greater levels of expression of progesterone-induced blocking factor protein than normal ovarian tissue according to immunohistochemistry. Further research is needed to understand the clinical importance of this finding, to learn outcomes of high levels of progesterone-induced blocking factor, and to investigate its underlying mechanisms.

CREB5 promotes tumor cell invasion and correlates with poor prognosis in epithelial ovarian cancer

CAMP responsive element binding protein 5 (CREB5) has crucial roles in regulating cell growth, proliferation, differentiation and cell cycle regulation. CREB5 has been identified to be overexpressed in several types of human cancer. However, the expression characteristics of CREB5 in epithelial ovarian cancer remains unknown, and its potential clinical prognostic significance has not yet been elucidated. In the present study, quantitative polymerase chain reaction (qPCR) and western blot analysis were performed to detect CREB5 mRNA and protein expression levels in 10 fresh tissue and cell lines epithelial ovarian cancer. Furthermore, CREB5 expression was analyzed using immunohistochemical analysis in 125 clinicopathologically characterized ovarian cancers: Stage I+II (n=31), stage III (n=70), stage IV (n=24). The patient survival rate was evaluated using Kaplan-Meier analysis. CREB5 was significantly overexpressed at both the mRNA and protein levels in epithelial ovarian cancer cells. There was a significant positive correlation between high CREB5 expression and increasing the International Federation of Gynecology and Obstetrics (FIGO) stage and pelvic lymph node metastasis (P<0.05). Patients with high CREB5 expression had a shorter overall survival, whereas patients with low CREB5 expression had longer survival. In addition, patients with high CREB5 expression had shorter relapse-free survival whereas patients with low CREB5 expression had longer relapse-free survival. Univariate logistic regression analysis and stepwise multivariate analysis all revealed that the FIGO stage and high CREB5 expression were significant risk factors for epithelial ovarian cancer (P<0.001), which suggested that CREB5 upregulation may be associated with a poor prognosis; therefore, it may be an independent prognostic indicator of epithelial ovarian cancer and may serve as a tumor-aggressive gene.

Abstract 5537: Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer

Abstract Integral membrane protein 2A (ITM2A) is a type 2 transmembrane protein of unknown function. The aim of this study was to investigate its expression pattern, clinical significance, and biological function in epithelial ovarian cancer. ITM2A expression in 35 normal, 20 adenoma, 11 borderline and 90 cancerous ovarian tissues was measured by immunohistochemistry. Clinicopathological parameters were obtained from medical records. Survival data was analyzed using Kaplan-Meier estimates and multivariate analysis using the Cox-regression method. Anti-tumor activities of ITM2A were explored by cell proliferation and colony formation assays, flow cytometry, Western blots and animal studies using ovarian cancer cell lines. Chemoresponsiveness was evaluated by measuring IC50 and confirmed by animal studies using an intraperitoneal orthotropic model. ITM2A was significantly downregulated in invasive carcinomas compared to normal, adenoma and borderline tumor tissues. ITM2A loss occurred in 45.6% (41 of 90) of invasive carcinomas and was significantly associated with FIGO stage, type II tumors, suboptimal debulking operation, recurrence and chemoresistance. ITM2A loss and higher FIGO stage were independent factors for poor prognosis. Expression of ITM2A inhibited growth and induced G2/M cell cycle arrest by attenuating cdc2, cyclin B1, cdc25c and p-cdc2 (Thr 161). In vitro and in vivo experiments showed that ITM2A expression significantly reduced the paclitaxel and carboplatin IC50 and tumor mass after paclitaxel treatment. ITM2A is a new biomarker of poor prognosis in ovarian cancer. It is a novel tumor suppressor that induces cell cycle arrest, acts as a chemosensitizer, and has therapeutic potential for ovarian cancer. Citation Format: So Young Kim, Eun-Ju Lee, Min Ji Cho, Hyemin Rhee. Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5537. doi:10.1158/1538-7445.AM2017-5537

Microbial infection, inflammation and epithelial ovarian cancer

Ovarian cancer is the most common, and life-threatening, type of female gynecological cancer. The etiology of ovarian cancer remains unclear, and there are currently no effective screening or treatment methods for the disease. Microbial infection serves a marked function in inducing carcinogenesis. A number of studies have identified pelvic inflammatory disease as a risk factor for epithelial ovarian cancer. Thus, it is hypothesized that microbial infection may contribute to ovarian cancer. In the present review, the microorganisms that have been identified to be associated with ovarian cancer and the underlying molecular mechanisms involved are discussed. Infection-induced chronic inflammation is considered an important process for carcinogenesis, cancer progression and metastasis. Therefore, the pathological process and associated inflammatory factors are reviewed in the present paper.

Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer

ObjectiveOvarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population. MethodsWe performed a case-control study of OCCC and HGSOC patients with and without VTE. 105 patients who underwent surgery at a tertiary care center between January 1995 and October 2013 were included. Plasma TF was measured with an enzyme-linked immunosorbent assay. A TF-dependent Factor Xa generation assay was used to measure MV TF activity. Immunohistochemical (IHC) analysis was performed to evaluate tumor expression of TF. Results35 women with OCCC or HGSOC diagnosed with VTE within 9months of surgery were included in the case group. Those with VTE had a worse OS, p<0.0001, with a greater than three-fold increase in risk of death, HR 3.33 (CI 1.75–6.35). There was no significant difference in median plasma TF level or MV TF activity level between patients with and without VTE. OCCC patients had greater expression of TF in their tumors than patients with HGSOC, p<0.0001. ConclusionsTFMV activity and plasma TF level were not predictive of VTE in this patient population. Given the extensive expression of TF in OCCC tumors, it is unlikely IHC expression will be useful in risk stratification for VTE in this population.

Expression and clinical significance of DNAJB11 in epithelial ovarian cancer

Objective: To study the expression of DNAJB11 protein in epithelial ovarian cancer tissues and its clinical significance. Methods: Immunohistochemistry was used to examine DNAJB11 expressions in 105 tissue specimens of ovarian epithelial carcinoma, 23 normal ovarian tissues, 17 tissues of benign tumor, and 13 tissues of of borderline tumor. The correlations between protein expression and clinicopathological factors were analyzed by Chi square test.The correlations between protein expression and survival were analyzed by Kaplan-Meier and Cox regression. Results: Positive expression of DNAJB11 protein was observed in 0.0% in normal ovary and benign tumor, 7.69% in borderline tumor, and 78.10% in epithelial ovarian cancer, respectively. Positive expression of DNAJB11 protein was significantly higher than the rest of the ovarian tissues and normal ovarian tissues (P<0.001).Higher expression of DNAJB11 was more prevalent in tissues from patients with advanced FIGO stages, high serum CA125, poor histological differentiation, and serous cancer. Kaplan-Meier curves revealed that higher expression of DNAJB11 was significantly associated with poor disease-free survival and overall survival.Multivariate survival analysis revealed that strong positive expression of DNAJB11 was an independent prognostic factor for disease-free survival and overall survival. Conclusion: DNAJB11 may play a role in tumorigenesis and progression of epithelial ovarian cancer.Strong positive expression of DNAJB11 was an independent prognostic factor in epithelial ovarian cancer.

The diagnostic efficacy of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in ovarian cancer

Platelet-to-lymphocyte (PLR) and Neutrophil-to-Lymphocyte (NLR) ratios have been extensively investigated in cancer. However, to date, actual guidelines concerning ovarian cancer are missing. The purpose of the present systematic review is to summarize the available evidence. We systematically searched Medline (1966-2016), Scopus (2004-2016), ClinicalTrials.gov (2008-2016), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2016) databases together with reference lists from included studies. Eighteen studies were included in the present systematic review that involved 3453 patients. According to the current data, both PLR and NLR values in ovarian cancer patients seem to deviate from healthy controls. Furthermore, they may also be indicative of the stage of the disease and of the response to chemotherapy. Nevertheless, their diagnostic accuracy remains limited as their sensitivity and specificity are moderate (detects 55-80% of ovarian cancer women). According to the findings of our study, both PLR and NLR seem to be promising screening and prognostic factors of epithelial ovarian cancer. The actual diagnostic cut-off values remain, however, undefined until now. Despite their limited sensitivity and specificity, they might be useful in the future as adjunct biomarkers for the detection and surveillance of the disease.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Preoperative multiplication of neutrophil and monocyte counts as a prognostic factor in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is leading cause of death in gynecologic cancer, and finding prognostic factors is important for establishing treatment plans. The aim of this study was to investigate the prognostic value of the multiplication of neutrophil and monocyte counts (MNM) in epithelial ovarian cancer (EOC). Data were retrospectively collected from Samsung Medical Center for EOC patients treated from January 2002 to December 2012. MNM was determined by multiplying neutrophil and monocyte counts and dividing by 10,000. Sensitivity and specificity of markers were assessed using receiver operating characteristic curves. We included 674 patients with EOC. For predicting overall survival (OS), the area under the curve for MNM was 0.607 (95% CI, 0.554-0.661) with sensitivity 55.2% and specificity 63.2% (cut-off value 197.40). The ability of MNM to determine OS was similar to that of the previously validated NLR and PLR. When the cohort was divided by cut-off values, poorer survival outcomes were observed in the group with higher MNM. Higher MNM was associated with advanced stage and presence of residual disease after primary treatment. Elevated pretreatment MNM is an independent predictor of poor survival and can be a useful biomarker in patients with EOC.

Expression of orphan GPR56 correlates with tumor progression in human epithelial ovarian cancer.

G protein-coupled receptor 56 (GPR56) has been demonstrated to be a significant prognostic predictor in several types of malignances, including melanoma, glioblastoma, breast cancer, colon cancer, and pancreatic cancer. GPR56 has a putative mucin-like extracellular domain, indicating functions for this receptor in the cell-cell interactions and triggering different downstream signaling pathways responsible for regulating cell survival, proliferation, adhesion, and migration. But the expression and clinical significance of GPR56 has not been elucidated in epithelial ovarian cancer (EOC). We detected GPR56 expression by immunohistochemistry in 110 samples of ovarian serous carcinoma to explore the correlation between its expression and clinicopathologic characteristics and overall survival. As the result, we found that GPR56 expression is significantly associated with advanced FIGO stage (P = 0.01) and positive lymph node invasion (P = 0.016), and it serves as an independent unfavorable prognostic factor through univariate and multivariate analysis. GPR56 knockdown could dramatically decrease the proliferation and invasion of epithelial ovarian cancer cells through down-regulating the RhoA-GTP level and up-regulating the E-cadherin level, which indicates GPR56 could promote the progression and invasion of EOC. In conclusion, GPR56 expression was demonstrated as an independent prognostic factor in EOC, suggesting that GPR56 may play an oncogenic role through the Rho and E-cadherin pathway and GPR56 could be a novel potential drug target in EOC.

Assessment of prognostic factors in epithelial ovarian cancer

Assessment of prognostic factors in epithelial ovarian cancer

The Association between Endometriosis, Tubal Ligation, Hysterectomy and Epithelial Ovarian Cancer: Meta-Analyses.

To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995–2016. Heterogeneity was evaluated by I2 statistic. Publication bias was tested by funnel plot and Egger’s test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28–1.57), tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60–0.81), while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81–1.14). A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer.

VEGF gene polymorphisms and outcome of epithelial ovarian cancer patients.

Since VEGF polymorphisms were associated with variable protein production, we analyzed herein their roles in outcome of epithelial ovarian cancer (EOC) patients. Genotypes of 85 patients with primary EOC were identified in DNA by real-time PCR. Progression-free survival and overall survival were analyzed using Kaplan-Meier method, univariate Cox model and bootstrap resampling study. At 60 months of follow-up, progression-free survival was shorter in patients with VEGF c.-2578 CC genotype compared with others (52.7 vs 82.2%; p = 0.04). Those patients had 2.15 more chance of presenting disease progression than others (p = 0.04); bootstrap study validated the result (p = 0.03). Our data suggest that VEGF c.-2578C>A polymorphism acts as a prognostic factor in EOC.