Identification of a gene expression signature for survival prediction in type I endometrial carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE21882 | GEO | 2011/05/17
SECONDARY ACCESSION(S): PRJNA126889
REPOSITORIES: GEO
Similar Datasets
Project description:Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favourable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and non-survivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were non-survivors. The tumours were analysed with genome-wide expression array analysis, represented by 13526 genes. Distinct differences in gene expression were found between the groups. A t-test established that a set of 218 genes were significantly differentially expressed (P < 0.001) between the two survival groups, and in a cross validation test 40 of the 45 (89%) tumours were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC>2) was added the hierachical clustering yielded similar results. Tumour cDNA from both groups (survivors vs. non-survivors) were hybridised together with the same reference, and we were able to calculate the relative expression level value for the sample Stage I tumours are expected to have a favourable prognosis. However, in our tumour material there were six non-survivors with stage I tumours. Five out of six stage I non-survivors clustered in the non-survival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.
2011-05-17 | E-GEOD-21882 | biostudies-arrayexpress
Project description:The clinical outcome for patients with ovarian cancer is difficult to predict. However, the use of biomarkers as additional prognostic factors may improve the outcome for these patients. In order to find novel candidate biomarkers, differences in gene expressions were analyzed in 54 stage III serous ovarian adenocarcinomas with oligonucleotide microarrays containing 27,000 unique probes. The microarray data was verified with quantitative real-time polymerase chain reaction for the genes TACC1, MUC5B and PRAME. With a hierarchical cluster analysis we detected a sub-group including 60% of the survivors. The gene expressions in tumours from patients in this sub-group of survivors were compared to the remaining tumours, and 204 genes were found to be differently expressed. We conclude that the sub-group of survivors might represent patients with favourable tumour biology and sensitivity to treatment. A selection of the 204 genes might be used as a predictive model to distinguish patients within and outside of this group. Alternative chemotherapy strategies could then be offered as first-line treatment, which could improve the clinical outcome for these patients. Keywords: Comparison between groups of samples 20 fresh frozen tumors from 5 year survivors were compared to 34 tumors from deceased patients in order to find genes where the expression differed between the two groups
2010-05-25 | E-GEOD-12418 | biostudies-arrayexpress
Project description:The clinical outcome for patients with ovarian cancer is difficult to predict. However, the use of biomarkers as additional prognostic factors may improve the outcome for these patients. In order to find novel candidate biomarkers, differences in gene expressions were analyzed in 54 stage III serous ovarian adenocarcinomas with oligonucleotide microarrays containing 27,000 unique probes. The microarray data was verified with quantitative real-time polymerase chain reaction for the genes TACC1, MUC5B and PRAME. With a hierarchical cluster analysis we detected a sub-group including 60% of the survivors. The gene expressions in tumours from patients in this sub-group of survivors were compared to the remaining tumours, and 204 genes were found to be differently expressed. We conclude that the sub-group of survivors might represent patients with favourable tumour biology and sensitivity to treatment. A selection of the 204 genes might be used as a predictive model to distinguish patients within and outside of this group. Alternative chemotherapy strategies could then be offered as first-line treatment, which could improve the clinical outcome for these patients. Keywords: Comparison between groups of samples
2008-08-12 | GSE12418 | GEO
Project description:Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Tumors are highly metastatic and long-term survival is poor. This study aims to investigate the prognosis associated gene expression profile in primary canine OS. Canine specific cDNA microarray representing 20,313 genes was used to analyze expression profiles in a panel of thirty-two primary osteosarcoma to identify genes associated with survival. The 32 tumours were classified into two groups of prognosis based on survival time (ST). They were defined as short survivors (dogs with poor prognosis that survived less than 6 months) and long survivors (dogs with better prognosis that survived longer than 6 months). Fifty-one genes were found to be differentially expressed, with common up regulation of these genes in the short survivors. The overexpression of these genes in short survivors suggests a possible role for increased proliferation, drug resistance or metastasis. Several deregulated pathways were identified in the present study includes Wnt signaling, Integrin signaling and Chemokine / cytokine signaling which were comparable to the pathway analysis conducted on human OS, adding more value for the dog as an excellent model to study human OS. Our results suggest that a molecular-based method for discrimination of outcome for short survivors and long survivors of canine OS may be useful for future prognostic stratification of dogs at initial diagnosis, where genes and pathways associated with cell cycle/ proliferation, drug resistance and metastasis could be potential targets for therapy that may not just be beneficial for dogs but also for humans.
2009-09-14 | GSE14033 | GEO
Project description:Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. Some of these patients may become long-term survivors. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression to trastuzumab. 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Sixty-five per cent of tumours were poorly differentiated ductal carcinomas and hormonal receptors were present in 47%. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median progression-free survival was 10.6 years after the diagnosis of metastatic disease. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival . Gene ontology analysis demonstrated that genes involved in HIF activation, EGF receptor signalling pathway, PI3 kinase pathway, apoptosis signalling pathway and p53 pathway significantly correlated with response. The PI3K pathway was the most strongly associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. These findings support that trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression to trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy. 53 FFPE samples, which passed the RNA quality control criteria, were analyzed (45 primary tumours and 8 metastases). Among these 53 samples, 35 samples corresponded to long-term responders and 18 to the control group.
2016-02-11 | E-GEOD-44272 | biostudies-arrayexpress
Project description:The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across 485,577 CpGs . Samples were restored FFPE DNA extracted from breast tumours in 3 groups; BRCA1 germline mutated tumours (BRCA1), BRCA1 germline wildtype tumours from women from high risk families (BRCAx) and the designated test variant tumours (BRCA1UV).
2016-03-01 | GSE72277 | GEO
Project description:Using gene expression microarrays, we tested whether lung SCCs that have metastasised to loco-regional lymph nodes (N1/2m) are different to those that directly invade and involve local nodes (N1d). Using 22,323 element microarrays, a non-parametric test identified 126 genes/transcripts that discriminated between N0 (n=35) and N1/2m (n=16) tumours (Wilcoxon-Mann-Whitney U test, P<0.01). Hiearchical clustering of all 59 tumours (including 8 N1d tumours) demonstrated the N1d tumours clustered with the N0 tumours rather than the N1/2m tumours. Next, we built class prediction models from the 35 N0 tumours and 16 N1/2m tumours to predict the class of N1d tumours. All models consistently classified N1d tumours as similar to N0 tumours. This could explain some of the variable response of some N1 tumours to adjuvant chemotherapy, and suggest refinement of the TNM "N" stage nomenclature to adjust for this biological observation to ensure appropriate patients benefit from treatment. Keywords: non-small cell lung carcinoma, squamous cell, nodal metastasis, TNM staging, expression profiling
2007-05-01 | GSE5828 | GEO
Project description:Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. Some of these patients may become long-term survivors. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression to trastuzumab. 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Sixty-five per cent of tumours were poorly differentiated ductal carcinomas and hormonal receptors were present in 47%. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median progression-free survival was 10.6 years after the diagnosis of metastatic disease. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival . Gene ontology analysis demonstrated that genes involved in HIF activation, EGF receptor signalling pathway, PI3 kinase pathway, apoptosis signalling pathway and p53 pathway significantly correlated with response. The PI3K pathway was the most strongly associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. These findings support that trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression to trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.
2016-02-11 | GSE44272 | GEO
Project description:Noncoding RNAs, especially microRNAs (miRNAs) have been implicated in the regulation of neuronal functions, such as learning, cognition and memory formation. However, the particular miRNAs involved in drug-induced behavioral plasticity are largely unknown. Here we report a novel regulator, miR-218, that inhibits heroin-induced behavioral plasticity. Network propagation-based method revealed several miRNAs that play key roles in drug-addiction, among which, miR-218 was decreased in nucleus accumbens (NAc) after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioning place preference (CPP) test and heroin self-administration (SA) experiment. Luciferase activity assay indicated miR-218 could regulate neuroplasticity related genes and directly target Mecp2 3’UTR. Consistently, Mecp2-/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, Mecp2, in the regulation of heroin-induced behavioral plasticity.
2017-03-08 | GSE89202 | GEO
Project description:Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and validated by non-negative matrix factorization . BACKGROUND: Current clinical and histopathological criteria used to define lung squamous cell carcinomas (SCCs) are insufficient to predict clinical outcome. We attempted to make a clinically-useful classification based on gene expression profiling. METHODS: We used cDNA microarrays with 40386 elements to analyze the gene expression profiles of 48 surgically resected samples of lung SCC. 9 samples of lung adenocarcinoma and 30 of normal lung were also included to give a total of 87 samples analyzed. After gene filtering, the data were subjected to hierarchical clustering and consensus clustering with the non-negative matrix factorization (NMF) approach. FINDINGS: Initial analysis by hierarchical clustering allowed division of SCCs into two distinct subclasses. An additional independent round of hierarchical clustering and consensus clustering with the NMF approach provided a validation for the classification. Kaplan-Meier analysis with the log rank test pointed to a non-significant difference in survival (p=0.071) but the likelihood of survival to 6 years was significantly different between the two groups (40.5% vs 81.8%, p=0.014, Z-test). Biological process categories characteristic for each subclass were identified statistically and up-regulation of cell-proliferation related genes was evident in the subclass with a poor prognosis. In the subclass with the better survival, genes involved in differentiated intracellular functions, such as the MAPKKK cascade, ceramide metabolism, or regulation of transcription, were up-regulated. Keywords: repeat sample
2009-04-01 | E-GEOD-2088 | biostudies-arrayexpress