PREDICTIVE MARKERS OF THE EFFICACY IN METASTATIC COLORECTAL TUMOR TREATED WITH CETUXIMAB - PHASE 2 STUDY
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colo-rectal Tumor,Metastatic Colon Cancer
PROVIDER: 2525001 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The aim of this study was to identify molecular markers able to classify osteosarcoma patients as good or poor responders before therapy. Methods: Gene expression profiling of 20 non-metastatic high-grade osteosarcoma patients was performed using cDNA nylon microarray which contained 8,032 unique sequenced-verified cDNA clones, representing 5,776 distinct genes. Expression of selected genes was validated using RTQ-PCR. For correlated genes, corresponding proteins were explored. Immunohistochemistry (IHC) on sections of tissue microarrays (TMA) were performed on a cohort of 50 patients, out of which 30 were new patients. Furthermore, fluorescent in situ hybridization (FISH) was performed on gene which could not be tested using IHC. Results: We have found that HSD17B10 gene expression was upregulated in the group of poor responders and that IHC expression of HSD17B10 in biopsy done before treatment was correlated to response to chemotherapy in 50 patients. Other relevant results include correlation of IFITM2, IFITM3 and RPL8 gene expression to response to chemotherapy. RPL8 gene expression also had a prognostic value for event-free survival. Moreover, a significant statistical correlation was found between polysomy 8 of RPL8 and good response to chemotherapy. Conclusion: These data suggest that HSD17B10 gene may be a biological marker and a therapeutic target in conventional osteosarcoma. This study highlights the prognostic and the predictive value of RPL8. RPL8 and IFITM2 may be useful in the assessment of patients with osteosarcoma at diagnosis and for stratifying patients taking part in randomized trials. Keywords: Gene-expression profiling
2010-02-15 | GSE11127 | GEO
Project description:The aim of this study was to identify molecular markers able to classify osteosarcoma patients as good or poor responders before therapy. Methods: Gene expression profiling of 20 non-metastatic high-grade osteosarcoma patients was performed using cDNA nylon microarray which contained 8,032 unique sequenced-verified cDNA clones, representing 5,776 distinct genes. Expression of selected genes was validated using RTQ-PCR. For correlated genes, corresponding proteins were explored. Immunohistochemistry (IHC) on sections of tissue microarrays (TMA) were performed on a cohort of 50 patients, out of which 30 were new patients. Furthermore, fluorescent in situ hybridization (FISH) was performed on gene which could not be tested using IHC. Results: We have found that HSD17B10 gene expression was upregulated in the group of poor responders and that IHC expression of HSD17B10 in biopsy done before treatment was correlated to response to chemotherapy in 50 patients. Other relevant results include correlation of IFITM2, IFITM3 and RPL8 gene expression to response to chemotherapy. RPL8 gene expression also had a prognostic value for event-free survival. Moreover, a significant statistical correlation was found between polysomy 8 of RPL8 and good response to chemotherapy. Conclusion: These data suggest that HSD17B10 gene may be a biological marker and a therapeutic target in conventional osteosarcoma. This study highlights the prognostic and the predictive value of RPL8. RPL8 and IFITM2 may be useful in the assessment of patients with osteosarcoma at diagnosis and for stratifying patients taking part in randomized trials. Keywords: Gene-expression profiling Gene expression profiling of 20 non-metastatic high-grade osteosarcoma patients was performed using spotted cDNA nylon membrane
2010-02-14 | E-GEOD-11127 | biostudies-arrayexpress
Project description:Background: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between HER2 positive and negative breast cancer tumors remain unclear. Objective: The aim of this study was to identify a gene expression profile for breast tumors based on HER2 status. Material and methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, as well as other genes located on 17q12, and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomics profiling to shed light on the molecular knowledge of HER2-positive breast tumors. The tumor samples under study correspond to 54 primary breast carcinomas. They included 15 cases with a HER2 IHC3+ score with HER2 gene amplification, 13 cases with IHC2+ score with amplification and 13 without HER2 gene amplification, and 13 cases IHC0/1+ score without HER2 gene amplification. 12 samples of breast normal tissues from breast cancer patients were also included as a reference. Neither overexpression nor amplification of HER2 was observed.
2011-12-22 | E-GEOD-29431 | biostudies-arrayexpress
Project description:The success of targeted therapies creates a need to discriminate tumors accurately by their histological and genetic characteristics. Here, we used cDNA microarray analysis to identify gene expression profiles and single markers that recapitulate the pathological and genetic background (i.e., BRAF, EGFR, KRAS, LKB1, PIK3CA, and TP53 gene alterations) of non-small cell lung cancer (NSCLC). Gene expression profiles were determined for 6 normal lung tissues and 69 lung tumors from patients diagnosed with NSCLC. We performed an unsupervised hierarchical clustering with the most variably expressed transcript to investigate whether there was evidence for natural grouping samples based on similarity in gene expression profiles. We examined the relationship between the clusters of tumors and patient and tumor characteristics such as gender, smoking status, histological type, degree of differentiation, tumor size, lymph node involvement and genetic background. We used a supervised analysis to identify the genes that are important for distinguishing subgroups of tumors defined by histological type. Moreover, we used this supervised approach to search for markers that characterize those tumors carrying EGFR, KRAS, PIK3CA and TP53 alterations. We identify several genes with characteristic patterns of expression in each tumor histological type (adenocarcinoma and squamous cell carcinoma) and we found that the presence of EGFR mutations result in a particular expression profile. Keywords: Transciption profiling of tumors with different histological and genetic background. We analyzed 69 NSCLC tumors. All the samples were characterized by histological type and by the presence of alterations at genes that are known to be involved in lung carcinogenesis. Mutational analysis of BRAF, EGFR, KRAS, and LKB1 is provided only for adenocarcinomas and analysis of alterations at PIK3CA gene (mutational analysis or gene amplification by FISH analysis) is provided only for 47 of the tumors. We analyzed gene expression profiles to identify those genes that are differentially expressed between two subgroups by t-test: 1) adenocarcinomas vs. squamous cell carcinomas; 2) tumors with mutation at EGFR gene vs. wild type tumors; 3) tumors with mutation at KRAS gene vs. wild type tumors; 4) tumors with mutation at TP53 gene vs. wild type tumors; 5) tumors with alterations (mutation or gene amplification) at PIK3CA gene vs. wild type tumors.
2008-07-22 | E-GEOD-8569 | biostudies-arrayexpress
Project description:Intimal sarcoma (IS) is a rare, malignant and aggressive tumor that shows a relentless course with a concomitant low survival rate, for which no effective treatment is available. In this study, 21 cases of large arterial blood vessel IS were analyzed by immunohistochemistry and fluorescent in situ hydridisation (FISH), and selectively by karyotyping, array-CGH, sequencing, phospho-kinase antibody arrays and Western immunoblotting, in search for the novel diagnostic markers and potential molecular targets. Ex vivo immunoassays were applied to test the sensitivity of IS primary tumor cells to the receptor tyrosine kinase (RTK) inhibitors imatinib and dasatinib.We demonstrated that amplification of the platelet-derived growth factor receptor alpha (PDGFRA) is a common finding in IS, and might be considered as a cytogenetic hallmark of this entity. This amplification is consistently associated with PDGFRA activation. Furthermore, the tumors reveal persistent activation of the epidermal growth factor receptor (EGFR), concurrent to PDGFRA activation. Activated PDGFRA and EGFR frequently co-exist with amplification and overexpression of MDM2. Ex vivo immunoassays on primary cells showed the potency of dasatinib to inhibit PDGFRA and downstream effectors in IS. Our findings provide a rationale for investigating therapies that target PDGFRA, EGFR or MDM2 in IS. Given the molecular heterogeneity of this tumor type and the potential crosstalk between PDGFRA and EGFR signaling pathways, targeting multiple RTKs and aberrant downstream effectors might be required to improve therapeutic outcome for patients with this disease. Key words: intimal sarcoma, PDGFRA, EGFR, MDM2, targeted therapy, amplification
2010-05-20 | GSE21530 | GEO
Project description:<h4><strong>INTRODUCTION:</strong> The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential.</h4><h4><strong>OBJECTIVES: </strong>The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O<sup>6</sup>-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time.</h4><h4><strong>METHODS:</strong> We applied <sup>1</sup>H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas.</h4><h4><strong>RESULTS:</strong> The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death.</h4><h4><strong>CONCLUSION:</strong> HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.</h4>
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2010-04-03 | E-GEOD-13439 | biostudies-arrayexpress