Circulating microRNAs as a fingerprint for endometrial endometrioid adenocarcinoma.

BACKGROUND: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and endometrial endometrioid adenocarcinoma (EEC) is the major histological type of endometrial cancer. There is a great need for better markers with high sensitivity and specificity to permit early diagnosis and proper management of EEC. The aim of our study is to identify a miRNA classifier within plasma as a noninvasive biomarker for EEC diagnosis. METHODS: This study was a retrospective case-control analysis which contained two independent cohorts including 93 participants. First, we screened 375 miRNAs in 29 plasma samples. 9 of the miRNAs were selected to be evaluated their expression by quantitative reverse-transcriptase polymerase chain reaction. A stepwise logistic regression model was then used to establish a new classifier in the validation cohort. Area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy. Co-expression analysis was used to verify the independence of results. RESULTS: miR-15b, -27a, and -223 were found to be differentially expressed in the EEC plasma between the two cohorts and had few connections with other miRNAs. The areas under the curve (AUC) were 0.768, 0.813, and 0.768 for miR-15b, -27a, and 223, respectively. miR-27a and CA125 can be combined as a potential non-invasive biomarker for detecting EEC, with the AUC of 0.894. CONCLUSION: Our study demonstrated three miRNAs, including miR-15b, -27a, and -233 have a good clinical value in EEC diagnosis. The classifier, including miR-27a and CA125, demonstrated a high accuracy in the diagnosis of EEC and might serve as a novel non-invasive biomarker in the future.

High expression of UCH37 is significantly associated with poor prognosis in human epithelial ovarian cancer.

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37) is a member of deubiquitinating enzymes. It can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. The aim of this study was to assess the value of UCH37 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the expression level of UCH37 in 5 paired EOC and normal tissue was tested by Western blot. And the association of UCH37 expression and prognostic value was analyzed in 100 tumor specimens from EOC patients, who underwent curative resection between 2003 and 2011. We found that UCH37 was up-regulated in most of the tumor tissue and high expression of UCH37 was an independent significant predictor associated with the poor outcome and recurrence of EOC (p=0.0037 and p=0.0042 in overall and disease-free survival, respectively), especially in the advanced stage of EOC (p=0.0106 and p=0.0115 in overall and disease-free survival, respectively), and may become a novel predictor for prognosis of EOC patients after curative resection. Our data suggest for the first time that UCH37 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients and may help physicians make informed decisions regarding adjuvant treatment following curative resection.

A ten-microRNA signature identified from a genome-wide microRNA expression profiling in human epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most common gynecologic malignancy. To identify the micro-ribonucleic acids (miRNAs) expression profile in EOC tissues that may serve as a novel diagnostic biomarker for EOC detection, the expression of 1722 miRNAs from 15 normal ovarian tissue samples and 48 ovarian cancer samples was profiled by using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. A ten-microRNA signature (hsa-miR-1271-5p, hsa-miR-574-3p, hsa-miR-182-5p, hsa-miR-183-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-182-3p, hsa-miR-141-5p, hsa-miR-130b-5p, and hsa-miR-135b-3p) was identified to be able to distinguish human ovarian cancer tissues from normal tissues with 97% sensitivity and 92% specificity. Two miRNA clusters of miR183-96-183 (miR-96-5p, and miR-182, miR183) and miR200 (miR-141-5p, miR200a, b, c and miR429) are significantly up-regulated in ovarian cancer tissue samples compared to those of normal tissue samples, suggesting theses miRNAs may be involved in ovarian cancer development.

Expression and clinical significance of BIRC6 in human epithelial ovarian cancer.

Baculoviral IAP repeat containing 6 (BIRC6), an unusually large member of the IAP family, may play an important role in oncogenesis. The aim of this study was to assess the value of BIRC6 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the differences of BIRC6 expression in four paired EOC and normal tissue were performed by Western blot, and expression of BIRC6 protein was analyzed in 100 clinicopathologically characterized EOC cases from those who underwent curative resection between 2003 and 2011 by immunohistochemistry. Kaplan-Meier survival estimates and log-rank tests were used to assess the prognostic significance. It was found that BIRC6 expression was higher in the carcinoma tissue than in normal control tissue at protein level by Western blot. There was a significant difference of BIRC6 expression in patients categorized according to tumor differentiation (p = 0.016). Univariate analyses and multivariate analyses revealed that BIRC6 was an independent significant predictor for overall survival and disease-free survival. A prognostic significance of BIRC6 was also found by Kaplan-Meier method. The expression of BIRC6 in the cytoplasm is associated with EOC differentiation and may be a novel predictor for poor prognosis of EOC patients after curative resection.