Double ratio of microRNA signatures as promising diagnosis biomarkers for mucinous borderline and malignant ovarian tumors
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PROVIDER: PRJNA1029619 | ENA |
REPOSITORIES: ENA
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Project description:Epithelial ovarian cancer (EOC) are a heterogeneous collection of malignancies, each with their own developmental origins, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis with a 5-year survival of 11% for advanced stages (III/IV). Clinically, due to the large size and heterogeneity of mu-cinous tumors, Malignant forms are difficult to distinguish from Borderline (15%) and benign (80%) forms with a better prognosis. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, miRNA expres-sion profiling generates using FFPE patient samples followed by qRT-PCR validation allows to identify 10 down-regulated and 5 up-regulated miRNAs between Malignant and Borderline tumors. To overcome issues linked to data normalization and to improve the accuracy of the results, a ratio analysis combining up-regulated and down-regulated miRNAs was used. Alt-hough 21/50 miRNA expression ratio were significantly different between Malignant and Bor-derline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 miRNAs expression ratio (double ratio) showed high discriminatory poten-tial, with 100% of accuracy in distinguishing Malignant and Borderline ovarian tumors, and suggests that miRNAs may hold significant clinical potential as a diagnostic tool. Epithelial ovarian cancer (EOC) are a heterogeneous collection of malignancies, each with their own developmental origins, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis with a 5-year survival of 11% for advanced stages (III/IV). Clinically, due to the large size and heterogeneity of mu-cinous tumors, Malignant forms are difficult to distinguish from Borderline (15%) and benign (80%) forms with a better prognosis. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, miRNA expres-sion profiling generates using FFPE patient samples followed by qRT-PCR validation allows to identify 10 down-regulated and 5 up-regulated miRNAs between Malignant and Borderline tumors. To overcome issues linked to data normalization and to improve the accuracy of the results, a ratio analysis combining up-regulated and down-regulated miRNAs was used. Alt-hough 21/50 miRNA expression ratio were significantly different between Malignant and Bor-derline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 miRNAs expression ratio (double ratio) showed high discriminatory poten-tial, with 100% of accuracy in distinguishing Malignant and Borderline ovarian tumors, and suggests that miRNAs may hold significant clinical potential as a diagnostic tool.
2023-10-19 | GSE245725 | GEO
Project description:Gene expression profile of 8 mucinous borderline ovarian tumors and 9 mucinous ovarian carcinomas. Frozen tumor samples were laser-capture microdissected for their epithelial component. RNA was extracted. Gene expression profiling was completed using Affymetrix U133 Plus 2.0 oligonucleotide microarrays.
2018-06-28 | E-MTAB-6844 | biostudies-arrayexpress
Project description:Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histological sub-type remains undetermined. While these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we performed high resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n=20) and borderline tumors (n=22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors performed to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways. Copy number data was generated for 42 mucinous ovarian tumours (20 benign, 22 borderline). Epithelial and stromal DNA from the tumours and matched-normal lymphocyte DNA were all analysed. Processed/normalized data for the germline DNA samples are not provided because they themselves are normalised to a diploid copy number, making all the probe values 2, which is not informative.
2012-08-26 | E-GEOD-39076 | biostudies-arrayexpress
Project description:Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histological sub-type remains undetermined. While these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we performed high resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n=20) and borderline tumors (n=22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors performed to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways.
2012-08-26 | GSE39076 | GEO
Project description:Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.
| S-EPMC10649586 | biostudies-literature
Project description:Mucinous cystic neoplasms (MCN) remain a major riddle in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and 6 hepatic MCNs (MCN-L). Unsupervised analysis of DNA methylation profiles of pancreatic neoplasms (11 entities and normal pancreatic tissue from 224 unique samples) revealed that MCN-P predominantly forms a distinct group. In the DNA methylation landscape of liver tumors, encompassing 5 tumor types and normal bile duct tissue from 136 unique samples, MCN-L demonstrated a specific methylation profile when compared to all other entities. Furthermore, within the DNA methylation landscape of ovarian tumors—featuring 5 tumor types, normal fallopian tube, and normal ovarian tissue from 90 unique samples—we found that both MCN-P and MCN-L grouped with mucinous ovarian carcinoma and mucinous borderline ovarian tumors. Notably, low-grade MCNs exhibited greater DNA methylation similarities to mucinous borderline ovarian tumors, while high-grade or invasive MCNs were primarily associated with mucinous ovarian carcinomas. When analyzing all samples together (19 tumor types and 4 normal tissue types, n = 430), MCNs similarly grouped with mucinous ovarian tumors and normal ovarian tissue. Additionally, in anetwork analysis of differentially methylated probes indicated that MCN-P and MCN-L share significant methylomic traits, closely resembling mucinous ovarian tumors. In conclusion, our findings highlight that MCN-P and MCN-L are distinct entities in the landscape of pancreatic and hepatic tumors and show DNA methylation profile similarities with mucinous ovarian tumors, suggesting a potential common origin.
2025-04-24 | GSE293725 | GEO
Project description:Mucinous colorectal adenocarcinoma
| PRJNA992109 | ENA
Project description:Mucus is associated with poor prognosis of colorectal cancer, but its mechanism remains unclear. The aim of this study was to reveal the key proteins in mucinous colorectal cancer. In this study, high-resolution liquid chromatography tandem mass spectrometry (LC-MS / MS) combined with quantitative 6-plex tandem mass mass tag labeling was used to profile protein changes in the left and right sides of mucinous and non-mucinous colorectal cancer tissues. A total of 7432 proteins were identified and analyzed.
2020-11-28 | PXD022802 |
Project description:Borderline disseminated intermediate cutaneous leishmaniasis
| PRJEB82932 | ENA
Project description:Transgenic mice (Scgb1a1-rtTA/[tetO]-KRAS.G12D/Nkx2-1+/-) develop mucinous lung tumors. Gene expression analysis was performed using mRNAs from the whole lungs of the mice compared to that of the control mice. We used microarrays to detail the global program of gene expression underlying development of mucinous lung tumors and identified distinct classes of up-regulated genes during this process. mRNAs were isolated from the whole lungs of the transgenic mice (Scgb1a1-rtTA/[tetO]-KRAS.G12D/Nkx2-1+/-) after 2 months doxycycline administration and hybridized on Affymetrix microarrays. We sought to identify genes induced in mucinous lung tumors.
2012-08-31 | E-GEOD-40508 | biostudies-arrayexpress