scholarly journals Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jun Li ◽  
Huiran Yue ◽  
Wenzhi Li ◽  
Guohua Zhu ◽  
Tingting Zhu ◽  
...  

Abstract Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Saisai Li ◽  
Xiaoli Hu ◽  
Miaomiao Ye ◽  
Xueqiong Zhu

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.


2020 ◽  
Author(s):  
Shahan Mamoor

High-grade serous ovarian cancer (HGSC) is the most common type of the most lethal gynecologic malignancy (1). To identify genes whose expression was associated with survival outcomes in HGSC, we used published data from patients enrolled in the ICON7 trial to compare the global gene expression profiles of primary HGSC tumors from women with the best and worst progression-free survival (PFS) (2). We found that the Frizzled class 7 (Fzd7) receptor was among the genes most differentially expressed in HGSC tumors when comparing tumor transcriptomes based on superior or inferior PFS. In two independent datasets, Fzd7 was among the genes most differentially expressed in HGSC tumors when comparing primary tumor to the normal ovary (3, 4). Wnt pathway signaling through Fzd7 may be relevant to the biology of high-grade serous ovarian cancers.


2019 ◽  
Vol 20 (18) ◽  
pp. 4533 ◽  
Author(s):  
András Penyige ◽  
Éva Márton ◽  
Beáta Soltész ◽  
Melinda Szilágyi-Bónizs ◽  
Róbert Póka ◽  
...  

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein–protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.


2015 ◽  
Vol 10 (3) ◽  
pp. 489
Author(s):  
Zhenhua Du ◽  
Xiaolin Ma

<p>We investigated dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin treatment on stage II-IV ovarian cancer patients. Between July, 2011, and October, 2014, a total of 221 patients was randomly assigned to receive dose-dense weekly paclitaxel and carboplatin group (n = 109) and conventional paclitaxel and carboplatin group (n = 112), just after the sixth chemotherapy cycles, and at 12 months after randomization. Median progression-free survival (PFS) was 16.8 months (range 3.3-48+ months) of conventional paclitaxel and carboplatin group was lower than that of dose-dense weekly paclitaxel and carboplatin group 27.6 months (range 4.2-51+ months). But, these clinical responses were not statistical significance in each group. In conclusion, dose-dense weekly paclitaxel and carboplatin treatment improves survival compared with conventional paclitaxel and carboplatin treatment. </p>


2021 ◽  
Author(s):  
Li Xia ◽  
Huang He

Abstract Backguound: To screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, in depth study of the potential mechanism of action of ovarian cancer, prediction of potential therapeutic targets and survival prognosis analysis of potential targets.Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients as the control group, and whole transcriptome of serum exosomes was performed to obtain differentially expressed lncRNA and mRNA in ovarian cancer,The miRcode database and miRNA target gene prediction website were used to predict the target genes, Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and the R language was used for GO and KEGG enrichment analysis of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival。Results: A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining mircode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4), and survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10 only genes, but not for the other genes, and through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.


2019 ◽  
Vol 31 (4) ◽  
pp. 645 ◽  
Author(s):  
Jihyun Kim ◽  
Jaewang Lee ◽  
Jin Hyun Jun

Recurrent implantation failure (RIF) is one of the main causes for the repeated failure of IVF, and the major reason for RIF is thought to be a miscommunication between the embryo and uterus. However, the exact mechanism underlying embryo–uterus cross-talk is not fully understood. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) among blastocysts, non-outgrowth and outgrowth embryos in mice using microarray analysis. A bioinformatics analysis was performed to predict the potential mechanisms of implantation. The miRNA expression profiles differed significantly between non-outgrowth and outgrowth embryos. In all, 3163 miRNAs were detected in blastocysts and outgrowth embryos. Of these, 10 miRNA candidates (let-7b, miR-23a, miR-27a, miR-92a, miR-183, miR-200c, miR-291a, miR-425, miR-429 and miR-652) were identified as significant differentially expressed miRNAs of outgrowth embryos by in silico analysis. The expression of the miRNA candidates was markedly changed during preimplantation embryo development. In particular, let-7b-5p, miR-200c-3p and miR-23a-3p were significantly upregulated in outgrowth embryos compared with non-outgrowth blastocysts. Overall, differentially expressed miRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos could be involved in embryo attachment, and interaction between the embryo proper and maternal endometrium during the implantation process.


Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 68483-68492 ◽  
Author(s):  
Liyuan Guo ◽  
Yan Peng ◽  
Yuanyuan Meng ◽  
Yunduo Liu ◽  
Shangshang Yang ◽  
...  

2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding SLIT and NTRK-like family member 3, SLITRK3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLITRK3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLITRK3 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SLITRK3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLITRK3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding sarcospan, SSPN, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SSPN expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SSPN expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SSPN is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SSPN may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding phosphodiesterase 5A, PDE5A, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. PDE5A expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. PDE5A expression correlated with progression-free survival in patients with p53 mutant ovarian cancer. These data indicate that expression of PDE5A is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. PDE5A may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


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