scholarly journals Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Li Ning ◽  
Jinghe Lang ◽  
Lingying Wu

Abstract Background Circular RNAs (circRNAs) are more stable than linear RNA molecules, which makes them promising diagnostic biomarkers for diseases. By circRNA-sequencing analysis, we previously found that circN4BP2L2 was significantly decreased in epithelial ovarian cancer (EOC) tissues, and was predictive of disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 in EOC. Methods Three hundred seventy-eight plasma samples were acquired prior to surgery. Samples were obtained from 126 EOC patients, 126 benign ovarian cyst patients, and 126 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). EOC cells were transfected with small interference RNAs (siRNAs) and cell proliferation, migration, invasion, cell cycle and cell apoptosis were performed to assess the effect of circN4BP2L2 in EOC. Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. Results Plasma circN4BP2L2 was significantly downregulated in EOC patients. Decreased circN4BP2L2 was significantly associated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC. CircN4BP2L2 inhibited tumor cell migration and invasion in vitro. CircN4BP2L2 could significantly separate EOC from benign (AUC = 0.82, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort. Early stage EOC vs benign (AUC = 0.81, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort could also be distinguished by circN4BP2L2. In discrimination between EOC cohort and benign or normal cohort, circN4BP2L2 performed equally well in both pre- and post-menopausal women. The combination of circN4BP2L2, CA125 and HE4 showed high sensitivity and specificity in detecting EOC cases. Conclusions Plasma circN4BP2L2 is significantly downregulated in EOC and might serve as a promising novel diagnostic biomarker for EOC patients, especially in early stage EOC cases. CircN4BP2L2 might act as an adjunct to CA125 and HE4 in detecting EOC. Further large-scale studies are warranted to verify our results.

2021 ◽  
Vol 10 (5) ◽  
pp. 1058
Author(s):  
Grégoire Rocher ◽  
Thomas Gaillard ◽  
Catherine Uzan ◽  
Pierre Collinet ◽  
Pierre-Adrien Bolze ◽  
...  

To determine if the time-to-chemotherapy (TTC) after primary macroscopic complete cytoreductive surgery (CRS) influences recurrence-free survival (RFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC). We conducted an observational multicenter retrospective cohort analysis of women with EOC treated from September 2006 to November 2016 in nine institutions in France (FRANCOGYN research group) with maintained EOC databases. We included women with EOC (all FIGO stages) who underwent primary complete macroscopic CRS prior to platinum-based adjuvant chemotherapy. Two hundred thirty-three patients were included: 73 (31.3%) in the early-stage group (ESG) (FIGO I-II), and 160 (68.7%) in the advanced-stage group (ASG) (FIGO III-IV). Median TTC was 43 days (36–56). The median OS was 77.2 months (65.9–106.6). OS was lower in the ASG when TTC exceeded 8 weeks (70.5 vs. 59.3 months, p = 0.04). No impact on OS was found when TTC was below or above 6 weeks (78.5 and 66.8 months, respectively, p = 0.25). In the whole population, TTC had no impact on RFS or OS. None of the factors studied were associated with an increase in TTC. Chemotherapy should be initiated as soon as possible after CRS. A TTC greater than 8 weeks is associated with poorer OS in patients with advanced stage EOC.


2015 ◽  
Vol 41 (4) ◽  
pp. 585-591 ◽  
Author(s):  
J.-Y. Lee ◽  
T.H. Kim ◽  
D.H. Suh ◽  
J.W. Kim ◽  
H.S. Kim ◽  
...  

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.


2021 ◽  
Author(s):  
Yingfeng Zhang ◽  
Yanhong Gao ◽  
Congcong Sun ◽  
Yanhua Mao ◽  
Benyuan Wu ◽  
...  

Abstract Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian tumours. In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of epithelial ovarian cancer were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in epithelial ovarian tumours and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with epithelial ovarian cancer was analysed with Kaplan–Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with a lentivirus. The anticancer activity of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT signalling pathway were differentially expressed in KIAA1456-overexpressing and control cells. Therefore, the biological function of HO8910PM cotransfected with KIAA1456- and SSX1-overexpressing cells was detected to validate the rescue effect of SSX1. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis, including p-AKT, PCNA, MMP9, CyclinD1 and Bcl-2, were detected by Western blot analysis.Results: KIAA1456 expression was lower in epithelial ovarian tumours than in normal ovarian tissues. Its expression level negatively correlated with pathological grade. Pearson’s correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. By contrast, the silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. Mechanistically, the overexpression of KIAA1456 inhibited SSX1 expression and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT signalling pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. Similarly, the silencing of KIAA1456 resulted in the opposite behaviour. Finally, SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for epithelial ovarian cancers.


Author(s):  
Risma Maharani ◽  
Syahrul Rauf ◽  
Rina Masadah

Objective: To determine the expression of Phosphatase Regenerating Liver-3 (PRL-3) and E-Cadherin in the epithelial ovarian cancer on various stages and differentiation grades. Method: This was a cross-sectional study design conducted at Obstetrics and Gynecology Department of several teaching hospitals, Faculty of Medicine Universitas Hasanuddin from January to June 2015. The expression of PRL-3 and E-cadherin was assessed immunohistochemically in 40 patients with epithelial ovarian cancer including 15 patients in early stage and 25 patients in advanced stage. We used the Fisher’s exact test with the significance of p0.05). The significant difference was found in the expression of E-cadherin whereas the high expression was shown at early stage than advanced stage (p0.05). This study also pointed out no correlation between the expression of PRL-3 and E-cadherin in epithelial ovarian cancer (p>0.05). Conclusion: PRL-3 overexpression does not decrease E-cadherin expression in epithelial ovarian cancer. Keywords: E-cadherin, epithelial ovarian cancer, PRL-3


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