Expression of retinoblatoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229598 | GEO | 2023/10/11
REPOSITORIES: GEO
Similar Datasets
Project description:Retinoblastoma (RB) is a malignant intraocular neoplasm occurs mostly in children. The malignancy caused due to altered miRNA expression in cancer tumors and circulating body fluids has been reported in several cancers. The aberrantly expressed microRNAs are useful for diagnosis and prognosticating the tumors. Circulating miRNAs have been identified as potential markers in neoplastic and non -neoplastic diseases. The aim of the study involves identifying microRNA signatures of serum of Retinoblastoma and possible use of differential miRNA as unique biomarker for RB. Agilent Single Color Whole miRNA microarray: 14 advanced stage Retinoblastoma Serum (pooled) Vs 14 Non-Retinoblastoma Serum (pooled) samples
2012-10-31 | E-GEOD-41321 | biostudies-arrayexpress
Project description:Retinoblastoma (RB) is a malignant intraocular neoplasm occurs mostly in children. The malignancy caused due to altered miRNA expression in cancer tumors and circulating body fluids has been reported in several cancers. The aberrantly expressed microRNAs are useful for diagnosis and prognosticating the tumors. Circulating miRNAs have been identified as potential markers in neoplastic and non -neoplastic diseases. The aim of the study involves identifying microRNA signatures of serum of Retinoblastoma and possible use of differential miRNA as unique biomarker for RB.
2012-10-31 | GSE41321 | GEO
Project description:5-methylcytosine (m5C) RNA modification installed by methyltransferase NSUN2 regulates gene expression and cell fate. Retinoblastoma (RB) is the most common primary intraocular tumor in children. However, the functional role of m5C modification in retinoblastoma remains unclear. Here, we show that 5-methylcytosine significantly promotes the progression of retinoblastoma. Retinoblastoma samples showed increased m5C levels, indicating a poor prognosis. Changes in global m5C modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, NSUN2 stabilized the methylated PFAS mRNA, a tumor promoter in retinoblastoma. Our work uncovers a critical function for m5C methylation in retinoblastoma and provides additional insight into the understanding of m5C modification.
2022-10-07 | GSE214685 | GEO
Project description:Background Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1-/- retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1-/- tumors seemed more dichotomous, differences within the RB1-/- tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared to tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation Molecular, clinical and histopathological differences between RB1-/- tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Fresh frozen material from 76 primary human retinoblastoma samples were profiled with Affymetrix human genome u133 plus 2.0 PM microarray
2015-07-01 | E-GEOD-59983 | biostudies-arrayexpress
Project description:Retinoblastoma (Rb), the most prevalent intraocular malignant tumor in children with global survival rate less than 30%, is mainly caused by the deficiency of the tumor suppressor RB1. A line of evidence have shown that local inflammation and immune escape play important roles in the occurrence of Rb, however the underlying mechanism remains unclear. We hypothesize that the unique neuroimmune cell type, retinal microglia, has a vital role in the Rb pathogenesis. In this study, we differentiated microglia cells (iMGs) from established induced pluripotent stem cells (iPSCs) derived from a retinoblastoma patient with the defined RB1 mutations. We investigated the function of RB1 in innate immune response of microglia and found that the expression of interleukins and chemokines, especially interleukin 6 and TNF-α, were highly upregulated in LPS-stimulated RB1 deficient iMGs, which enhanced innate immune responses and created a pro-inflammation environment. These findings demonstrated that RB1 is indispensable to maintain microglia function in innate immunity and its deficiency leads to enhanced inflammation responses, which may accelerate tumor growth and malignancy. This study provides new insights for pathological mechanism and immunotherapeutic target of retinoblastoma.
2022-12-31 | GSE212248 | GEO
Project description:Retinoblastoma (Rb) is the most common intraocular tumor in childhood and represent a very robust model about hereditary develop for cancer. We believe that miRNome expression may give clues to understanding Rb heterogeneity and to comprehend biological features in order to find new biomarkers for better treatments. We explore 12 Rb tumors from enucleated patients with no chemotherapy history from Children Hospital of Mexico Federico Gomez and Pediatric Hospital Medical Center XXI century by informed parental consent to collaborate with retrospective research. 5 bilateral and 7 unilateral, 4 female and 8 male samples were tailed and labeled with biotin to hybridize in GeneChip miRNA 4.0 Affymetrix array. Chips were washed and scanned 18hrs after hybridization.
2017-07-11 | E-MTAB-4977 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) provide a platform for understanding mechanisms underlying diseases and finding ways to treat them. Trilateral retinoblastoma (TRb) is a condition in which retinoblastoma, the most common congenital intraocular malignancy, is associated with an intracranial neural tumor. This mostly fatal disease is caused by biallelic inactivation of the retinoblastoma-1 (RB1) gene, transcribing pRB. Using CRISPR-Cas9 we generated RB1-null hESCs, an embryonic lethal condition. These cells display distinct gene expression patterns with alterations in pRB targets, and mitochondrial phenotypes similar to those of poorly differentiated retinoblastomas. RB1–/– hESC produce extremely large teratomas, with neural expansions similar to those of TRb tumors. Analysis of these tumors revealed a potentially novel role of pRB in ectoderm differentiation, acting through ZEB1. Lastly, RB1–/– cells are significantly sensitive to carboplatin, a chemotherapy used to treat TRb, suggesting our model can be used to screen novel treatments for the disease.
2017-04-09 | GSE84504 | GEO
Project description:Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 primary breast cancer patients of the Oslo2 study was cut and blended before being divided into fractions for DNA-, RNA- and protein isolation, and metabolomics, allowing for representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results: Based on DNA copy number data, tumors were scored into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and using integrative clustering, tumors were classified into ten subtypes. The final consensus clustering incorporating all the aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype where these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significant different outcome, and in another a trend was observed. Conclusions: The herein identified six integrated subtypes confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing the knowledge of the luminal A subtype heterogeneity may add pivotal information guiding therapeutic choices, evidently bringing us closer to more personalized treatment for this largest subgroup of breast cancer.
2017-03-01 | GSE81000 | GEO
Project description:Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 primary breast cancer patients of the Oslo2 study was cut and blended before being divided into fractions for DNA-, RNA- and protein isolation, and metabolomics, allowing for representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results: Based on DNA copy number data, tumors were scored into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and using integrative clustering, tumors were classified into ten subtypes. The final consensus clustering incorporating all the aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype where these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significant different outcome, and in another a trend was observed. Conclusions: The herein identified six integrated subtypes confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing the knowledge of the luminal A subtype heterogeneity may add pivotal information guiding therapeutic choices, evidently bringing us closer to more personalized treatment for this largest subgroup of breast cancer.
2017-03-01 | GSE80999 | GEO
Project description:Retinoblastoma (Rb) is the most prevalent intraocular malignant tumor in children with less than 30% survival rate globally. Rb genetic predisposition has been well defined for decades, whereas its developmental origin and drug agents remain largely unexplored. Here we developed the first organoidal retinoblastoma model derived from human embryonic stem cells (hESCs) with a biallelic knockout (RB1-/-) or mutagenesis (RB1Mut/Mut) of the RB1 gene, which exhibit extreme consistent properties of Rb tumorigenesis, transcriptome, and genome-wide methylation. Using single-cell RNA-seq and immunostaining of this model, we found that developmentally Rb originated from ARR3+ maturing cone precursors and a new cell type of unfolded protein response occurred in the organoidal retinoblastoma. A key PI3K-Akt pathway was aberrantly regulated, and its strong activator SYK (encoding proto-oncogenic spleen tyrosine kinase) was significantly upregulated in the cancerous organoids. Furthermore, we demonstrated that the SYK inhibitors, A502 and B502, have more significant therapeutic response on the early-stage organoidal retinoblastoma compared to four well-established chemotherapeutic drugs in clinic. Collectively, we established a brand-new organoidal retinoblastoma model derived from human ESCs in-a-dish and discovered its cell-of-origin and potential drug agents, shedding light on development and therapeutics of human cancers.
2020-09-05 | GSE136929 | GEO