scholarly journals Molecular Profiling Predicts the Existence of Two Functionally Distinct Classes of Ovarian Cancer Stroma

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Loukia N. Lili ◽  
Lilya V. Matyunina ◽  
L. DeEtte Walker ◽  
Benedict B. Benigno ◽  
John F. McDonald
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Cancer Development ◽  
Tissue Samples ◽  
Cancer Stroma ◽  
Expression Platform ◽  
Gene Expression Platform ◽  
Genes Encoding ◽  
Ovarian Surface Epithelial

Although stromal cell signaling has been shown to play a significant role in the progression of many cancers, relatively little is known about its importance in modulating ovarian cancer development. The purpose of this study was to investigate the process of stroma activation in human ovarian cancer by molecular analysis of matched sets of cancer and surrounding stroma tissues. RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133 Plus 2.0) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of ovarian cancer patients (Cepi) and matched sets of surrounding cancer stroma (CS). For controls, ovarian surface epithelial cells (OSE) were isolated from the normal (noncancerous) ovaries and normal stroma (NS). Hierarchical clustering of the microarray data resulted in clear separations between the OSE, Cepi, NS, and CS samples. Expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples indicate the existence of two subgroups of cancer stroma (CS) with different propensities to support tumor growth. Our results indicate that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.

scholarly journals Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation

2021 ◽  
Vol 22 (12) ◽  
pp. 6216
Author(s):  
Monika Englert-Golon ◽  
Mirosław Andrusiewicz ◽  
Aleksandra Żbikowska ◽  
Małgorzata Chmielewska ◽  
Stefan Sajdak ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Control Group ◽  
Tissue Samples ◽  
Altered Expression ◽  
Depth Study ◽  
Tyrosine Protein Kinase ◽  
Ovarian Tumorigenesis ◽  
Protein Immunoreactivity

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.

scholarly journals NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinzhuan Jia ◽  
Lan Wei ◽  
Zhengmao Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Expression Patterns ◽  
Chemotherapy Resistance ◽  
Direct Interaction ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Qrt Pcr

BackgroundAccumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.PurposeOur aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.MethodsThe expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and SOX3. Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.ResultsIn this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed in vivo. Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted SOX3 mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.ConclusionNEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/SOX3 pathway, showing that NEAT1 might be a potential target for OC resistance treatment.

scholarly journals Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

2019 ◽  
Vol 20 (18) ◽  
pp. 4533 ◽  
Author(s):  
András Penyige ◽  
Éva Márton ◽  
Beáta Soltész ◽  
Melinda Szilágyi-Bónizs ◽  
Róbert Póka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Cancer Development ◽  
Plasma Samples ◽  
Circulating Mirna ◽  
Differentially Expressed Mirnas ◽  
Potential Biomarkers

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.

scholarly journals Identification of Gene Expression Pattern Related to Breast Cancer Survival Using Integrated TCGA Datasets and Genomic Tools

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Zhenzhen Huang ◽  
Huilong Duan ◽  
Haomin Li
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Clinical Data ◽  
Cancer Genomics ◽  
Expression Patterns ◽  
Gene List ◽  
Gene Expression Pattern ◽  
Cancer Development

Several large-scale human cancer genomics projects such as TCGA offered huge genomic and clinical data for researchers to obtain meaningful genomics alterations which intervene in the development and metastasis of the tumor. A web-based TCGA data analysis platform called TCGA4U was developed in this study. TCGA4U provides a visualization solution for this study to illustrate the relationship of these genomics alternations with clinical data. A whole genome screening of the survival related gene expression patterns in breast cancer was studied. The gene list that impacts the breast cancer patient survival was divided into two patterns. Gene list of each of these patterns was separately analyzed on DAVID. The result showed that mitochondrial ribosomes play a more crucial role in the cancer development. We also reported that breast cancer patients with low HSPA2 expression level had shorter overall survival time. This is widely different to findings of HSPA2 expression pattern in other cancer types. TCGA4U provided a new perspective for the TCGA datasets. We believe it can inspire more biomedical researchers to study and explain the genomic alterations in cancer development and discover more targeted therapies to help more cancer patients.

Tissue Microarray Detection of Estrogen Receptor, Progesterone Receptor, and C-erbB-2 in Patients with Ovarian Cancer and a Preliminary Study on the Molecular Typing of Ovarian Cancer

2020 ◽  
Vol 12 (10) ◽  
pp. 1159-1165
Author(s):  
Jian Wang ◽  
Dehua Liu ◽  
Yong Liu ◽  
Gongliang Zhang ◽  
Fang Peng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Molecular Typing ◽  
Expression Patterns ◽  
Double Positive ◽  
Cancer Subtypes ◽  
Er Expression

We evaluated the expression of estrogen receptor (ER), progesterone receptor (PR), and C-erbB-2 in patients with ovarian cancer using tissue microarrays (TMA) and preliminarily analyzed molecular typing data. Specimens from 119 ovarian cancer patients were collected and were analyzed by TMA. The expression of ER, PR, and C-erbB-2 was examined by IHC and the clinicopathological associations were analyzed. The results indicated that higher ER expression was observed in SC and EC, whereas PR exhibited a similar expression pattern, but relatively lower compared with ER expression. Conversely, very weak expression was observed in CCC and MC, especially for PR (All P <0.05). C-erbB-2 exhibited no expression pattern differences among the different histological types (All P >0.05), but exhibited higher positive expression in FIGO III and IV stages, whereas there was no difference in ER and PR expression among the different stages. Higher PR expression was observed in middle and highly differentiated tumors, whereas higher C-erbB-2 expression was associated with low degree of differentiation (P <0.05). Patients with ER (+) PR (+) C-erbB-2 (?) had a better prognosis and patients with ER (?) PR (?) C-erbB-2 (+) had the worst prognosis. In conclusion, ER and PR tend to be highly expressed in less malignant ovarian cancer subtypes such as SC and EC. Ovarian cancer patients with ER/PR double-positive and C-erbB-2 negative expression patterns survive longer.

Expression of CD24 in plasma, exosome and ovarian tissue samples of serous ovarian cancer patients

2019 ◽  
Vol 298 ◽  
pp. 16-20 ◽  
Author(s):  
Beáta Soltész ◽  
János Lukács ◽  
Edina Szilágyi ◽  
Éva Márton ◽  
Melinda Szilágyi Bónizs ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Ovarian Tissue ◽  
Serous Ovarian Cancer ◽  
Tissue Samples

scholarly journals Overexpression ofGPC6andTMEM132Din Early Stage Ovarian Cancer Correlates with CD8+ T-Lymphocyte Infiltration and Increased Patient Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Athanasios Karapetsas ◽  
Antonis Giannakakis ◽  
Denarda Dangaj ◽  
Evripidis Lanitis ◽  
Spyridon Kynigopoulos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
T Lymphocyte ◽  
Early Stage ◽  
Mrna Levels ◽  
Lymphocyte Infiltration ◽  
Ovarian Cancer Cell Lines ◽  
Cd8 T Lymphocyte ◽  
Genes Encoding ◽  
Early Stage Ovarian Cancer

Infiltration of cytotoxic T-lymphocytes in ovarian cancer is a favorable prognostic factor. Employing a differential expression approach, we have recently identified a number of genes associated with CD8+ T-cell infiltration in early stage ovarian tumors. In the present study, we validated by qPCR the expression of two genes encoding the transmembrane proteins GPC6 and TMEM132D in a cohort of early stage ovarian cancer patients. The expression of both genes correlated positively with the mRNA levels ofCD8A, a marker of T-lymphocyte infiltration [Pearson coefficient: 0.427 (p=0.0067) and 0.861 (p<0.0001), resp.].GPC6andTMEM132Dexpression was also documented in a variety of ovarian cancer cell lines. Importantly, Kaplan-Meier survival analysis revealed that high mRNA levels of GPC6 and/or TMEM132D correlated significantly with increased overall survival of early stage ovarian cancer patients(p=0.032). Thus,GPC6andTMEM132Dmay serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis, prognosis, and tumor immunobattling.

Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients

2009 ◽  
Vol 114 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Ram Eitan ◽  
Michal Kushnir ◽  
Gila Lithwick-Yanai ◽  
Miriam Ben David ◽  
Moshe Hoshen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Microrna Expression ◽  
Platinum Based Chemotherapy

scholarly journals ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1137
Author(s):  
Wenyu Wang ◽  
Jihye Im ◽  
Soochi Kim ◽  
Suin Jang ◽  
Youngjin Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Histone Deacetylases ◽  
Expression Patterns ◽  
Ros Generation ◽  
Class Iii ◽  
Cancer Hallmarks ◽  
Cancer Cell Death ◽  
Platinum Based Chemotherapy

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III NAD+ dependent histone deacetylases (HDACs), has been reported to be involved in regulating cancer hallmarks including drug response. In this study, we aimed to identify the role of SIRT2 in oxidative stress and cisplatin response in cancer. Two ovarian cancer cell lines featuring different sensitivities to cisplatin were used in this study. We found different expression patterns of SIRT2 in cisplatin-sensitive (A2780/S) and cisplatin-resistant (A2780/CP) cancer cells with cisplatin treatment, where SIRT2 expression was augmented only in A2780/S cells. Furthermore, cisplatin-induced ROS generation was responsible for the upregulation of SIRT2 in A2780/S cells, whereas overexpression of SIRT2 significantly enhanced the sensitivity of cisplatin-resistant counterpart cells to cisplatin. Our study proposes that targeting SIRT2 may provide new strategies to potentiate platinum-based chemotherapy in ovarian cancer patients.

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