Applied Biosystems Human TaqMan Low Density Array (TLDA) in plasma samples from EOC cases and controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50472 | GEO | 2013/08/30
SECONDARY ACCESSION(S): PRJNA217691
REPOSITORIES: GEO
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Project description:Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC. We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validationsets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients. Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis. We designed a multi-stage, retrospective, nested case-control study to determine whether serum miRNA profiles can be used to predict EOC development. All samples were grouped into screening, training, and validation sets. A total of 560 plasma samples (360 cases and 200 controls) were obtained from Tianjin Medical University Cancer Institute and Hospital (TCIH) and Cancer Center of Nanjing Medical University. The cases and controls were well matched for age. The International Federation of Gynaecology and Obstetrics (FIGO) staging system was used to stage cases. All patients and controls were genetically unrelated, ethnic Han Chinese women who were permanent residents of the urban area of Tianjin and Nanjing. Controls with cardiovascular, respiratory, digestive, urinary, reproductive, and endocrine diseases were excluded. The study protocols were approved by the Tianjin and Nanjing Center review committees. In screening set, to detect generalizable miRNA signatures, we pooled serum samples of 10 early-stage cases (stage I), 10 late-stage cases (stage IIIc-IV), and 10 healthy controls, respectively, and analyzed these three pool samples using a TaqMan low-density array (TLDA set 2.0, Applied Biosystems) chip screening in the discovery stage. In training set, the miRNAs identified in the screening set were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on individual plasma samples of 76 EOC patients and 30 normal controls. In validation set, the validation set comprised a two-phase process. Promising associations from the screening and training set were evaluated in the validation phase I set, comprising 134 cases and 70 controls from Tianjin Center. The validation phase II set included samples of 77 EOC cases and 50 normal controls were from Tianjin Center and 73 EOC cases and 50 normal controls were from Nanjing Center.
2013-08-30 | E-GEOD-50472 | biostudies-arrayexpress
Project description:The aim of the presented study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC), and to investigate miRNA profiles in regard to clinicopathological characteristics of the tumors. Results: qPCR validation revealed regulation of 14 miRNAs in EEC tissues (miR-9, miR-141,miR-205,miR-203,miR-183,miR-200a*,miR-200b*,miR-200a,miR-200c,miR-429,miR-200b,miR-410,miR-92a,miR-1305) and 9 in plasma samples (miR-449a,miR-1290,miR-1228,miR-203,miR-200a,miR-141,miR-92a, miR-9, miR-301b). Expression of certain miRNAs showed association with FIGO stage, grade and relapse. Two miRNA signatures, miR-205/miR-410 and miR-410/miR-429/miR-92a, classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC 0.972, 95% CI 0.919-0.995 and 0.991, 95% CI 0.948-1.000, resepctively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR 2.98) and progression-free survival (miR-1228/miR-429, HR 4.149). Plasma miRNA signatures classified EEC plasma samples with high accuracy. Conclusions: We conclude that miRNA signatures hold great promise for becoming non-invasive biomarkers for early EEC detection and prognosis.
2012-06-01 | GSE35794 | GEO
Project description:The aim of the presented study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC), and to investigate miRNA profiles in regard to clinicopathological characteristics of the tumors. Results: qPCR validation revealed regulation of 14 miRNAs in EEC tissues (miR-9, miR-141,miR-205,miR-203,miR-183,miR-200a*,miR-200b*,miR-200a,miR-200c,miR-429,miR-200b,miR-410,miR-92a,miR-1305) and 9 in plasma samples (miR-449a,miR-1290,miR-1228,miR-203,miR-200a,miR-141,miR-92a, miR-9, miR-301b). Expression of certain miRNAs showed association with FIGO stage, grade and relapse. Two miRNA signatures, miR-205/miR-410 and miR-410/miR-429/miR-92a, classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC 0.972, 95% CI 0.919-0.995 and 0.991, 95% CI 0.948-1.000, resepctively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR 2.98) and progression-free survival (miR-1228/miR-429, HR 4.149). Plasma miRNA signatures classified EEC plasma samples with high accuracy. Conclusions: We conclude that miRNA signatures hold great promise for becoming non-invasive biomarkers for early EEC detection and prognosis. Tissue samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Of 24 samples analyzed by microarrays, 22 (18 EEC, 4 normal controls) were available for final analysis. Expression of 14 miRNAs was analysed in 48 plasma samples by qPCR.
2012-05-31 | E-GEOD-35794 | biostudies-arrayexpress
Project description:The paper describes a model on the detection of cancer based on cancer and immune biomarkers.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Improving cancer detection through combinations of cancer and immune biomarkers: a modelling approach
Raluca Eftimie and and Esraa Hassanein
J Transl Med (2018) 16:73
Abstract:
Background: Early cancer diagnosis is one of the most important challenges of cancer research, since in many can- cers it can lead to cure for patients with early stage diseases. For epithelial ovarian cancer (which is the leading cause of death among gynaecologic malignancies) the classical detection approach is based on measurements of CA-125 biomarker. However, the poor sensitivity and specificity of this biomarker impacts the detection of early-stage cancers.
Methods: Here we use a computational approach to investigate the effect of combining multiple biomarkers for ovarian cancer (e.g., CA-125 and IL-7), to improve early cancer detection.
Results: We show that this combined biomarkers approach could lead indeed to earlier cancer detection. However, the immune response (which influences the level of secreted IL-7 biomarker) plays an important role in improving and/or delaying cancer detection. Moreover, the detection level of IL-7 immune biomarker could be in a range that would not allow to distinguish between a healthy state and a cancerous state. In this case, the construction of solu- tion diagrams in the space generated by the IL-7 and CA-125 biomarkers could allow us predict the long-term evolu- tion of cancer biomarkers, thus allowing us to make predictions on cancer detection times.
Conclusions: Combining cancer and immune biomarkers could improve cancer detection times, and any predic- tions that could be made (at least through the use of CA-125/IL-7 biomarkers) are patient specific.
Keywords: Ovarian cancer, Mathematical model, CA-125 biomarker, IL-7 biomarker, Cancer detection times
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2024-09-02 | BIOMD0000000741 | BioModels
Project description:Epithelial ovarian cancer (EOC) is the type of ovarian cancer having the highest mortality rate. Because of the asymptomatic characteristic and a few diagnostic tests, it is mostly diagnosed at advanced stages. Therefore, this study aims to gain the predictive and/or early diagnostic novel circulating miRNAs for EOC. Firstly, microarray analysis of miRNA expression level is performed on plasma samples from pathologically confirmed EOC patients and matching healthy individuals; EOC tissue samples and benign ovarian neoplastic tissues. 31 significantly dysregulated miRNAs in serum and 3 miRNAs in tissue were identified by microarray. The results were validated using RT-qPCR. KEGG database was used for the target gene and pathway analysis. Three miRNA from EOC serum (hsa-miR-1909-5p, hsa-miR-885-5p, hsa-let-7d-3p) and one microRNA from tissue samples (hsa-miR-200c-3p) were validated as significant enough to distinguish EOC patients from healthy individuals. KEGG pathway enrichment analysis showed 7 significant pathways, which are prion diseases, proteoglycans in cancer, oxytocin signaling pathway, hippo signaling pathway, adrenergic signaling in cardiomyocytes, oocyte meiosis, and thyroid hormone signaling pathway, in which our validated miRNAs have a role. It supports our hypothesis that several miRNAs, in our case validated 4 miRNAs, can have the potential to be a biomarker of EOC diagnosis and treatment.
2023-02-24 | GSE216150 | GEO
Project description:Objective: The immune system is a key player in fighting cancer. Thus, we seeked to identify a molecular ‘immune response signature’ indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC. Methods: Comparing the expression of 32,000 genes in a leukocytes fraction from 48 EOC patients and 20 controls, three uncorrelated shrunken centroid models were selected, comprised of 7, 14, and 6 genes. A second selection step using RT-qPCR data and significance analysis of microarrays yielded 13 genes which were finally used in 343 samples (90 healthy, 6 cystadenoma, 8 low malignant potential tumor, and 239 EOC patients). Using new 65 controls and 224 EOC patients the abundances of six plasma proteins was determined and used in combination with the expression values from the 13 genes for diagnosis of EOC. Results: Combined diagnostic models using either each five gene expression and plasma protein abundance values or 13 gene expression and six plasma protein abundance values can discriminate controls from patients with EOC with Receiver Operator Characteristics Area Under the Curve values of 0.998 and bootstrap .632+ validated classification errors of 3.1% and 2.8%, respectively. The sensitivities were 97.8% and 95.6%, respectively, at a set specificity of 99.6%. Conclusion: The combination of expression based and plasma protein based biomarkers in one diagnostic model increases the sensitivity and the specificity significantly. Such a diagnostic test may allow earlier diagnosis of epithelial ovarian cancer. The expression of a blood cell fraction from 20 healthy controls and 48 patients with epithelial ovarian cancer was compared.
2011-09-01 | E-GEOD-31682 | biostudies-arrayexpress
Project description:Objective: The immune system is a key player in fighting cancer. Thus, we seeked to identify a molecular ‘immune response signature’ indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC. Methods: Comparing the expression of 32,000 genes in a leukocytes fraction from 48 EOC patients and 20 controls, three uncorrelated shrunken centroid models were selected, comprised of 7, 14, and 6 genes. A second selection step using RT-qPCR data and significance analysis of microarrays yielded 13 genes which were finally used in 343 samples (90 healthy, 6 cystadenoma, 8 low malignant potential tumor, and 239 EOC patients). Using new 65 controls and 224 EOC patients the abundances of six plasma proteins was determined and used in combination with the expression values from the 13 genes for diagnosis of EOC. Results: Combined diagnostic models using either each five gene expression and plasma protein abundance values or 13 gene expression and six plasma protein abundance values can discriminate controls from patients with EOC with Receiver Operator Characteristics Area Under the Curve values of 0.998 and bootstrap .632+ validated classification errors of 3.1% and 2.8%, respectively. The sensitivities were 97.8% and 95.6%, respectively, at a set specificity of 99.6%. Conclusion: The combination of expression based and plasma protein based biomarkers in one diagnostic model increases the sensitivity and the specificity significantly. Such a diagnostic test may allow earlier diagnosis of epithelial ovarian cancer.
2011-09-02 | GSE31682 | GEO
Project description:We profile expression in serous epithelial ovarian carcinomas to assess the possibility of an miRNA signature associated with chemoresistance. Resistance to the available therapies is one of the main causes of low survival of patients with advanced epithelial ovarian cancer, thus representing an emergency in oncology. Here, we profiled miRNA expression in 86 naïve serous epithelial ovarian carcinomas (EOCs) to assess the possibility of miRNAs associated with chemoresistance. We identified 23 miRNAs associated with chemoresistance, of which three (miR-484, miR-642 and miR-217) were confirmed in the validation set (112 independent patients). The study of miR-484 role demonstrated that it regulated the chemoresistance of EOC cells acting not on cancer cells but on tumor vasculature. In particular, miR-484 is produced and secreted by chemosensitive EOC, therefore regulating the production of VEGFB by cancer cells and the expression of VEGFR2 in endothelial cells. Overall, we demonstrated that a three-miR signature can classify the response to chemotherapy and that chemoresistance in EOC relays, at least in part, on the control of tumor angiogenesis, indicating new options in the treatment of these patients. We analyzed tumor samples (<5% of normal tissue) from FFPE blocks of 86 patients with serous ovarian carcinomas.
2013-05-17 | E-GEOD-43867 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in gene regulation and their dysregulation is associated with many diseases. In this study, we determined the expression and function of miR-590-3p in EOC. We found that miR-590-3p levels were higher in high-grade carcinoma when compared to low-grade or tumours with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in EOC patients than in subjects with benign gynaecological disorders. Transient transfection of miR-590-3p mimics, or stable transfection of mir-590, increased cell growth, migration, and invasion. In vivo studies revealed that mir-590 accelerated tumour growth and metastasis. Using a cDNA microarray, we identified Forkhead box A2 (FOXA2) and Versican (VCAN) as a top downregulated and a top upregulated gene, respectively, by mir-590. We showed that miR-590-3p targeted FOXA2 3’ UTR to suppress its expression. In addition, knockdown of FOXA2 by siRNAs or knockout of FOXA2 by CRISPR/Cas9 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, while knockout of FOXA2 increased, VCAN mRNA and protein levels and ChIP-qPCR revealed that FOXA2 binds to VCAN promoter. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumours and that high FOXA2/low VCAN mRNA levels in tumours were positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2-VCAN pathway.
2018-04-21 | GSE113440 | GEO
Project description:We profile expression in serous epithelial ovarian carcinomas to assess the possibility of an miRNA signature associated with chemoresistance. Resistance to the available therapies is one of the main causes of low survival of patients with advanced epithelial ovarian cancer, thus representing an emergency in oncology. Here, we profiled miRNA expression in 86 naïve serous epithelial ovarian carcinomas (EOCs) to assess the possibility of miRNAs associated with chemoresistance. We identified 23 miRNAs associated with chemoresistance, of which three (miR-484, miR-642 and miR-217) were confirmed in the validation set (112 independent patients). The study of miR-484 role demonstrated that it regulated the chemoresistance of EOC cells acting not on cancer cells but on tumor vasculature. In particular, miR-484 is produced and secreted by chemosensitive EOC, therefore regulating the production of VEGFB by cancer cells and the expression of VEGFR2 in endothelial cells. Overall, we demonstrated that a three-miR signature can classify the response to chemotherapy and that chemoresistance in EOC relays, at least in part, on the control of tumor angiogenesis, indicating new options in the treatment of these patients.
2013-05-17 | GSE43867 | GEO