Saisai Li

Correlation between estrogen receptor expression and prognosis in epithelial ovarian cancer: a meta-analysis

OBJECTIVE Accumulated studies have investigated the prognostic significance of estrogen receptor expression in epithelial ovarian cancer, but results remain controversial. The aim of this study was to perform a meta-analysis to clarify the prognostic value of estrogen receptor expression in epithelial ovarian cancer. METHODS A systematic search was performed in PUBMED, EMBASE, and COCHRANE databases to identify relevant studies up to December 2016. The pooled hazard rates (HR) with 95% confidence intervals (CIs) for overall survival and time to tumor progression were calculated and then weighted and pooled in this meta-analysis with a random-effect model. RESULTS Thirty-five studies with a total of 5824 patients were included. In brief, the expression of estrogen receptor was associated with an improved overall survival (HR = 0.86, 95% CI = 0.76-0.97), whereas there was no significant difference between estrogen receptor and time to tumor progression among epithelial ovarian cancer patients. Subgroup analysis revealed that estrogen receptor expression was significantly correlated with overall survival in different subgroups, such as in unclassified epithelial ovarian cancer (HR= 0.80, 95% CI = 0.66-0.95), studies using immunohistochemistry detection method (HR= 0.85, 95% CI = 0.73-1.00), European population (HR= 0.75, 95% CI = 0.60-0.94) and estrogen receptor α subtype (HR= 0.78, 95% CI = 0.62-0.98). CONCLUSIONS Estrogen receptor, especially estrogen receptor α, was associated with an improved overall survival in epithelial ovarian cancer. Estrogen receptor expression may be a promising prognostic factor in epithelial ovarian cancer patients.Objective Accumulated studies have investigated the prognostic significance of estrogen receptor expression in epithelial ovarian cancer, but results remain controversial. The aim of this study was to perform a meta-analysis to clarify the prognostic value of estrogen receptor expression in epithelial ovarian cancer. Methods A systematic search was performed in PUBMED, EMBASE, and COCHRANE databases to identify relevant studies up to December 2016. The pooled hazard rates (HR) with 95% confidence intervals (CIs) for overall survival and time to tumor progression were calculated and then weighted and pooled in this meta-analysis with a random-effect model. Results Thirty-five studies with a total of 5824 patients were included. In brief, the expression of estrogen receptor was associated with an improved overall survival (HR = 0.86, 95% CI = 0.76-0.97), whereas there was no significant difference between estrogen receptor and time to tumor progression among epithelial ovarian cancer patients. Subgroup analysis revealed that estrogen receptor expression was significantly correlated with overall survival in different subgroups, such as in unclassified epithelial ovarian cancer (HR= 0.80, 95% CI = 0.66-0.95), studies using immunohistochemistry detection method (HR= 0.85, 95% CI = 0.73-1.00), European population (HR= 0.75, 95% CI = 0.60-0.94) and estrogen receptor α subtype (HR= 0.78, 95% CI = 0.62-0.98). Conclusions Estrogen receptor, especially estrogen receptor α, was associated with an improved overall survival in epithelial ovarian cancer. Estrogen receptor expression may be a promising prognostic factor in epithelial ovarian cancer patients.

Prognostic values of excision repair cross-complementing genes mRNA expression in ovarian cancer patients

&NA; Excision repair cross‐complementing (ERCC) genes, key components of the nucleotide excision repair pathway, are regarded as crucial factors for DNA repair capacity. Previous studies have investigated prognostic values of ERCC genes in a number of malignancies. However, the relationship between ERCC genes and prognosis of ovarian cancer patients remains controversial. Therefore, in the current study, we systematically analyze the prognostic values of ERCC genes in ovarian cancer by the Kaplan‐Meier plotter, which includes updated gene expression data and survival information of 1656 ovarian cancer patients. Our results showed that high expression of ERCC1 and ERCC8 mRNA was related to a worse overall survival among ovarian cancer patients, especially in late stage and poor differentiation serous ovarian patients. Increased ERCC4 mRNA expression indicated a better overall survival among serous ovarian cancer patients. The other ERCC genes were uncorrelated with prognosis in ovarian cancer. These results indicate that some ERCC genes have critical prognostic values in ovarian cancer.

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis

Objective While a prognosis value of progesterone receptor (PR) in ovarian cancer has been reported in some publications, controversial data were presented by different reports. In order to address the disagreement of progesterone receptor in ovarian cancer survival, we conducted this meta-analysis. Methods Relevant articles on progesterone receptor and ovarian cancer prognosis were identified via a thorough search of PubMed, Embase and Cochrane Central. Hazard ratios (HR) and 95% confidence interval (CI) were extracted from studies on overall survival (OS) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS). Result A total of 28 eligible studies containing 5685 patients were collected for analysis. It was found that progesterone receptor positivity was significantly associated with favorable overall survival (OS) (HR = 0.86, 95% CI = 0.78 to 0.95, P = 0.002) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS) (HR = 0.75, 95% CI = 0.61 to 0.93, P = 0.008) of ovarian cancer patients. Subgroup analysis showed that progesterone receptor expression was associated with a favorable prognosis of unclassified ovarian cancer, European origin, and immunohistochemical detection method. Conclusion Progesterone receptor expression can be used as a favorable prognostic predictor in ovarian cancer managements.

The prognostic values of the peroxiredoxins family in ovarian cancer

Purpose: Peroxiredoxins (PRDXs) are a family of antioxidant enzymes with six identified mammalian isoforms (PRDX1–6). PRDX expression is up-regulated in various types of solid tumors; however, individual PRDX expression, and its impact on prognostic value in ovarian cancer patients, remains unclear. Methods: PRDXs family protein expression profiles in normal ovarian tissues and ovarian cancer tissues were examined using the Human Protein Atlas database. Then, the prognostic roles of PRDX family members in several sets of clinical data (histology, pathological grades, clinical stages, and applied chemotherapy) in ovarian cancer patients were investigated using the Kaplan–Meier plotter. Results: PRDXs family protein expression in ovarian cancer tissues was elevated compared with normal ovarian tissues. Meanwhile, elevated expression of PRDX3, PRDX5, and PRDX6 mRNAs showed poorer overall survival (OS); PRDX5 and PRDX6 also predicted poor progression-free survival (PFS) for ovarian cancer patients. Furthermore, PRDX3 played significant prognostic roles, particularly in poor differentiation and late-stage serous ovarian cancer patients. Additionally, PRDX5 predicted a lower PFS in all ovarian cancer patients treated with Platin, Taxol, and Taxol+Platin chemotherapy. PRDX3 and PRDX6 also showed poor PFS in patients treated with Platin chemotherapy. Furthermore, PRDX3 and PRDX5 indicated lower OS in patients treated with these three chemotherapeutic agents. PRDX6 predicted a poorer OS in patients treated with Taxol and Taxol+Platin chemotherapy. Conclusion: These results suggest that there are distinct prognostic values of PRDX family members in patients with ovarian cancer, and that the expression of PRDX3, PRDX5, and PRDX6 mRNAs are a useful prognostic indicator in the effect of chemotherapy in ovarian cancer patients.

Prognostic values of aquaporins mRNA expression in human ovarian cancer

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0–12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using ‘Kaplan–Meier plotter’ (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members’ mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.

Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy

PurposeDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR has been reported as a prognostic marker in certain cancers; however, the results are controversial. Therefore, identification of the prognostic value of MMR genes in ovarian cancer based on a large sample size is pivotal.MethodsIn the current study, we systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum-based chemotherapy through “The Kaplan–Meier plotter” (KM plotter) database, which contains gene expression data and survival information of ovarian cancer patients.ResultsAmong seven MMR genes, high mRNA levels of MSH6, MLH1 and PMS2 were significantly associated with a better overall survival for all ovarian cancer patients treated with platinum-based chemotherapy, especially in late-stage and poor-differentiated ovarian cancer patients. Increased MSH6 and PMS2 mRNA expression was correlated with a favorable overall survival in serous ovarian cancer patients.ConclusionsOur results indicate that sufficient MMR system is associated with an improved survival in ovarian cancer treated with platinum-based chemotherapy. MMR gene may be a potential prognosis predictor in ovarian cancer.

Effect of vitamin E supplementation on uterine cervical neoplasm: A meta-analysis of case-control studies

Several epidemiological studies have suggested that vitamin E could reduce the risk of uterine cervical neoplasm. However, controversial data were presented by different reports. Hence, we conducted a meta-analysis to assess the relationship between vitamin E and the risk of cervical neoplasia. We performed a comprehensive search of the PubMed, Embase and Cochrane databases through December 31, 2016. Based on a fixed-effects or random-effects model, the odds ratio (OR) and 95% confidence intervals (CIs) were calculated to assess the combined risk. Subgroup analyses and meta-regression were done to assess the source of heterogeneity. Subgroup analyses were performed according to survey ways, types of cervical neoplasia, study populations. A protocol was registered with PROSPERO (No. CRD42016036672). In total, 15 case-control studies were included, involving 3741 cases and 6328 controls. Our study suggested that higher category of vitamin E could reduce the cervical neoplasia risk (OR = 0.58, 95% CIs = 0.47–0.72, I2 = 83%). In subgroup-analysis, both vitamin E intake and blood levels of vitamin E had a significant inverse association with the risk of cervical neoplasm. Additionally, we found the same relationship between vitamin E and cervical neoplasia among different populations and types of cervical neoplasia. Meta-regression showed that none of the including covariates were significantly related to the outcomes. No evidence of publication bias was observed. In conclusion, vitamin E intake and blood vitamin E levels were inversely associated with the risk of cervical neoplasia.

The prognostic values of signal transducers activators of transcription family in ovarian cancer

Signal transducer and activator of transcription (STAT), a family of latent cytoplasmic transcription factors, are composed of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). STATs are associated with several biological processes such as cell proliferation, invasion, and metastasis in various cancer types. In addition, the STAT family has been well studied as a prognostic predictor for a considerable number of solid tumors. However, the prognostic value of the STAT family in ovarian cancer patients remains unclear. In our present study, we intend to access the prognostic roles of the STAT family in ovarian carcinoma through the ‘Kaplan–Meier plotter’ (KM plotter) online database, which collected gene expression data and survival information (overall survival (OS)) from a total of 1582 ovarian cancer patients. Our results show that high mRNA expression of STAT1, STAT4, STAT5a, STAT5b, and STAT6, are correlated to a better OS of ovarian cancer patients, especially the high level of STAT1 and STAT4 are significantly related to a favorable OS for serous ovarian cancer patients. We further accessed the prognostic roles of individual STATs in other clinicopathological features, such as pathological grades, clinical stages, and TP53 mutation, and found that these genes indicate a favorable prognosis especially for late stage, poor differentiation, and TP53 mutated ovarian cancer patients. In conclusion, these results suggest that the STAT family plays a significant prognostic role in ovarian carcinoma and individual STATs, except STAT2 and STAT3, may act as favorable prognostic markers in ovarian cancer.

Predictive Role of Galectin-1 and Integrin α5β1 in Cisplatin-based Neoadjuvant Chemotherapy of Bulky Squamous Cervical Cancer

Although galectin-1 and integrin α5β1 confer chemoresistance to certain types of cancer, whether their expression predicts the response to cisplatin-based neoadjuvant chemotherapy (NACT) in squamous cervical cancer remains unclear. Paired tumor samples (pre- and post-chemotherapy) were obtained from 35 bulky squamous cervical cancer patients treated with cisplatin-based NACT and radical hysterectomy at our hospital between January 2007 and August 2014. The expression of galectin-1 and integrin α5β1 in tumor cells and stromal cells was analyzed by immunohistochemistry. The correlation between galectin-1/integrin α5β1 and apoptosis-associated markers was investigated by using the The Cancer Genome Atlas (TCGA) RNA-sequencing data. Seventeen patients were identified as chemotherapy responders and 18 as non-responders. Galectin-1 and integrin α5β1-positive immunostaining was more frequently observed in stromal cells than its in tumor cells. The expression of galectin-1 and integrin α5β1 in stromal and tumor cells was significantly down-regulated in postchemotherapy cervical cancer tissues. High levels of galectin-1 and integrin α5β1 in stromal were associated with a negative chemotherapy response in squamous cervical cancer patients treated with cisplatin-based NACT. Additionally, the expression of galectin-1 and integrin α5 correlated negatively with caspase 3/caspase 8 by using the TCGA RNA-sequencing data. Galectin-1 and integrin α5β1 expression in stromal may serve as a prediction of the responses to cisplatin-based NACT for patients with bulky squamous cervical cancer. Galectin-1 and integrin α5β1 may be implicated in the development of chemoresistance in cervical cancer via suppressing apoptosis.