Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome analysis reveals molecularly distinct subtypes in retinoblastoma.

ABSTRACT: Retinoblastoma is the most frequent intraocular malignancy in children. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using gene expression profiles, we demonstrate the existence of two major retinoblastoma subtypes that can be divided into six subgroups. Subtype 1 has higher expression of cone related genes and higher percentage of RB1 germline mutation. By contrast, subtype 2 tumors harbor more genes with ganglion/neuronal features. The dedifferentiation in subtype 2 is associated with stemness features including low immune infiltration. Gene Otology analysis demonstrates that immune response regulations and visual related pathways are the key molecular difference between subtypes. Subtype 1b has the highest risk of invasiveness across all subtypes. The recognition of these molecular subtypes shed a light on the important biological and clinical perspectives for retinoblastomas.

SUBMITTER: Zeng Q

PROVIDER: S-EPMC10542806 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Transcriptome analysis reveals molecularly distinct subtypes in retinoblastoma.

Zeng Qi Q Wang Sha S Chen Lu L Wang Jinwei J

Scientific reports 20230930 1

Retinoblastoma is the most frequent intraocular malignancy in children. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using gene expression profiles, we demonstrate the existence of two major retinoblastoma subtypes that can be divided into six subgroups. Subtype 1 has higher expression of cone related genes and higher percentage of RB1 germline mutation. By contrast, subtype 2 tumors harbor more genes with ganglion/neuronal features ...[more]

PMID: 37777551

Similar Datasets

Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme.

Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes more highly expressed in rapidly progressing tumors that stratified GBMs into two groups that differed by >4-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus identify and validate a prognostic marker of both biologic and clinical significance and provide a series of putative markers for additional evaluation.

| S-EPMC556127 | biostudies-literature

Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme

Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Using regression correlation

2006-01-18 | E-GEOD-4058 | biostudies-arrayexpress

Molecularly distinct striatonigral neuron subtypes differentially regulate locomotion.

Project description:Striatonigral neurons, traditionally known for promoting locomotion, comprise diverse subtypes with distinct transcriptomic profiles. However, their specific contributions to locomotor regulation remain incompletely understood. Using the genetic markers Kremen1 and Calb1, we demonstrate in mouse models that Kremen1+ and Calb1+ striatonigral neurons exerted opposing effects on locomotion. Kremen1+ neurons displayed delayed activation at locomotion onset but exhibited increasing activity during locomotion offset. In contrast, Calb1+ neurons showed early activation at locomotion onset and decreasing activity during locomotion offset. Optogenetic activation of Kremen1+ neurons suppressed ongoing locomotion, whereas activation of Calb1+ neurons promoted locomotion. Activation of Kremen1+ neurons induced a greater reduction in dopamine release than Calb1+ neurons, followed by a post-stimulation rebound. Conversely, activation of Calb1+ neurons triggered an initial increase in dopamine release. Furthermore, genetic knockdown of GABA-B receptor Gabbr1 in Aldh1a1+ nigrostriatal dopaminergic neurons (DANs) reduced DAN inhibition and completely abolished the locomotion-suppressing effect of Kremen1+ neurons. Together, these findings reveal a cell type-specific mechanism within striatonigral neuron subtypes: Calb1+ neurons promote locomotion, while Kremen1+ neurons terminate ongoing movement by inhibiting Aldh1a1+ DAN activity via GABBR1 receptors.

| S-EPMC11923167 | biostudies-literature

Integrative Transcriptome Analysis Reveals Common Molecular Subtypes of Human Hepatocellular Carcinoma

Project description: Not available

| S-DIXA-D-1002 | biostudies-other

Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme

2006-01-19 | GSE4058 | GEO

Integrative multi-omic analysis identifies new drivers and pathways in molecularly distinct subtypes of ALS.

Project description:Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease. Increasing the chances of success for future clinical strategies requires more in-depth knowledge of the molecular basis underlying disease heterogeneity. We recently laid the foundation for a molecular taxonomy of ALS by whole-genome expression profiling of motor cortex from sporadic ALS (SALS) patients. Here, we analyzed copy number variants (CNVs) occurring in the same patients, by using a customized exon-centered comparative genomic hybridization array (aCGH) covering a large panel of ALS-related genes. A large number of novel and known disease-associated CNVs were detected in SALS samples, including several subgroup-specific loci, suggestive of a great divergence of two subgroups at the molecular level. Integrative analysis of copy number profiles with their associated transcriptomic data revealed subtype-specific genomic perturbations and candidate driver genes positively correlated with transcriptional signatures, suggesting a strong interaction between genomic and transcriptomic events in ALS pathogenesis. The functional analysis confirmed our previous pathway-based characterization of SALS subtypes and identified 24 potential candidates for genomic-based patient stratification. To our knowledge, this is the first comprehensive "omics" analysis of molecular events characterizing SALS pathology, providing a road map to facilitate genome-guided personalized diagnosis and treatments for this devastating disease.

| S-EPMC6620285 | biostudies-literature

Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes.

Project description:A major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair cells and supporting cell types remains unresolved. Here, we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair cells and non-sensory supporting cells. We identify a putative progenitor population for hair cells and supporting cells, as well as distinct hair and supporting cell types in the maculae versus cristae. The hair cell and supporting cell types differ from those described for the lateral line system, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the three macular organs, the utricle, saccule, and lagena, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals validate zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.

| S-EPMC9851615 | biostudies-literature

Early-stage serrated adenocarcinomas are divided into several molecularly distinct subtypes.

Project description:Serrated adenocarcinoma (SAC) is considered the end stage of the serrated neoplasia pathway. Although SAC prognosis is not widely recognized, the serrated pathway-associated subtype consistently exhibits unfavorable prognosis in genetic studies. Herein, we classified molecularly distinct subtypes of serrated adenocarcinomas and clarified their associated clinicopathological characteristics and genetic changes. We examined 38 early-stage colorectal SACs. Of these, 24 were classified into three molecularly distinct groups by colon cancer subtyping (CCS). The clinicopathological characteristics, Ki 67 labeling index (LI), and SAC epithelial serration were assessed. The DNA from carcinomas and normal tissue/adenoma was extracted by laser microdissection and sequenced by next-generation sequencing, and mutation numbers and patterns of a 15-oncogene panel were determined. The CCS groups included CCS1 (CDX2+, HTR2B-, FRMD6-, ZEB1-, and microsatellite instable-low [MSI-L]/microsatellite stable [MSS]; 14 cases), CCS2 (microsatellite instable-high [MSI-H], 5 cases), and CCS3 (CDX2-, HTR2B+, FRMD6+, ZEB1+, and MSI-L/MSS; 5 cases). Invasive cancer was significantly more frequent in CCS3 than in CCS1 (5/5 versus 3/14, respectively). Ki67 LI and epithelial serration were higher in CCS3 than in CCS1 (83.0 ± 5.8 versus 65.4 ± 4.0 and 5/5 versus 3/14, respectively; p = 0.031 and 0.0048). CCS2 showed the highest mutation number, whereas KRAS and BRAF mutation numbers were higher in CCS3 than in CCS1. Early-stage SACs were classified into three molecularly distinct subtypes with different clinicopathological and genetic characteristics.

| S-EPMC6382106 | biostudies-literature

Transcriptome analysis reveals TMPRSS6 isoforms with distinct functionalities.

Project description:TMPRSS6 (matriptase-2) is a type II transmembrane serine protease involved in iron homoeostasis. At the cell surface of hepatocytes, TMPRSS6 cleaves haemojuvelin (HJV) and regulates the BMP/SMAD signalling pathway leading to production of hepcidin, a key regulator of iron absorption. Although four TMPRSS6 human isoforms and three mice Tmprss6 isoforms are annotated in databases (Ensembl and RefSeq), their relative expression or activity has not been studied. Analyses of RNA-seq data and RT-PCR from human tissues reveal that TMPRSS6 isoform 1 (TMPRSS6-1) and 3 are mostly expressed in human testis while TMPRSS6-2 and TMPRSS6-4 are the main transcripts expressed in human liver, testis and pituitary. Furthermore, we confirm the existence and analyse the relative expression of three annotated mice Tmprss6 isoforms. Using heterologous expression in HEK293 and Hep3B cells, we show that all human TMPRSS6 isoforms reach the cell surface but only TMPRSS6-1 undergoes internalization. Moreover, truncated TMPRSS6-3 or catalytically altered TMPRSS6-4 interact with HJV and prevent its cleavage by TMPRSS6-2, suggesting their potential role as dominant negative isoforms. Taken together, our results highlight the importance of understanding the precise function of each TMPRSS6 isoforms both in human and in mouse.

| S-EPMC5867103 | biostudies-literature

Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.

Project description:Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes.Unsupervised hierarchical clustering analysis was applied to gene expression data from 177 patients with colorectal cancer to determine a prognostic gene expression signature. Validation of the signature was sought in two independent patient groups. The association between the signature and prognosis of patients was assessed by Kaplan-Meier plots, log-rank tests and the Cox model.The authors identified a gene signature that was associated with overall survival and disease-free survival in 177 patients and validated in two independent cohorts of 213 patients. In multivariate analysis, the signature was an independent risk factor (HR 3.08; 95% CI 1.33 to 7.14; p=0.008 for overall survival). Subset analysis of patients with AJCC (American Joint Committee on Cancer) stage III cancer revealed that the signature can also identify the patients who have better outcome with adjuvant chemotherapy (CTX). Adjuvant chemotherapy significantly affected disease-free survival in patients in subtype B (3-year rate, 71.2% (CTX) vs 41.9% (no CTX); p=0.004). However, such benefit of adjuvant chemotherapy was not significant for patients in subtype A.The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.

| S-EPMC3419333 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data