Gene expression analysis of canine osteosarcoma tissue from patients with normal and increased serum alkaline phosphatase concentration
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE63476 | GEO | 2014/11/19
SECONDARY ACCESSION(S): PRJNA268017
REPOSITORIES: GEO
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Project description:Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, though its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumors or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, DCUN1D1 was increased in both the tissue and cell lines of the normal ALP group. Using QPCR, differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells. A total of 18 canine primary osteosarcoma tumor samples were used in this study. 9 tumor samples were from patients having a normal serum alkaline phosphatase concentration. 9 tumor samples were from patients having an increased serum alkaline phosphatase concentration. There were no reference tissues or controls used in this study.
2014-11-19 | E-GEOD-63476 | biostudies-arrayexpress
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells.
2014-05-22 | GSE57884 | GEO
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells. A total of six canine primary osteosarcoma cell lines were used in this study. Three cell lines were capable of forming tumors when transplanted into mice (tumorigenic) and three cell lines were not capable of forming tumors upon transplant into mice (non-tumorigenic). The gene expression data is from the primary cell lines, not the transplanted cells. There were no reference cell lines or controls used in this study.
2014-05-22 | E-GEOD-57884 | biostudies-arrayexpress
Project description:Interventions: Injection of HER2 vaccine
Primary outcome(s): Serum HER2 concentration Tumor marker concentrations
Study Design: Single arm Non-randomized
| 2739306 | ecrin-mdr-crc
Project description:Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types. The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. Significance: This is the first large scale study of DNA methylation in osteosarcoma and lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of different genomic landscapes.
2020-05-01 | GSE149679 | GEO
Project description:Background: Dilated cardiomyopathy (DCM) is the most common acquired heart disease in large- and giant-breed dogs with Doberman Pinschers representing one of the most frequently affected breeds. MicroRNAs (miRNAs) are short non-coding RNAs which play important roles in gene regulation. Different miRNA expression patterns have been described for human DCM and might represent potential diagnostic markers. There are no studies to date investigating miRNA expression profiles in canine DCM. Goals: The goals of this study were to screen the miRNAs expression profile of canine serum by using a miRNA microarray platform and to compare the miRNA expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results: Although total RNA concentrations were very low in canine serum samples, 421 different miRNAs were detectable with sufficient signal intensity on the miRNA microarrays. About 30 miRNAs were differentially expressed in the two groups, but did not reach statistical significance. No significant differences were found using specific miRNA PCR assays. Conclusions: More than 400 miRNAs can be detected in canine serum samples. Changes in expression levels of various miRNAs between healthy and DCM dogs could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases
2013-03-22 | GSE36976 | GEO
Project description:Background: Dilated cardiomyopathy (DCM) is the most common acquired heart disease in large- and giant-breed dogs with Doberman Pinschers representing one of the most frequently affected breeds. MicroRNAs (miRNAs) are short non-coding RNAs which play important roles in gene regulation. Different miRNA expression patterns have been described for human DCM and might represent potential diagnostic markers. There are no studies to date investigating miRNA expression profiles in canine DCM. Goals: The goals of this study were to screen the miRNAs expression profile of canine serum by using a miRNA microarray platform and to compare the miRNA expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results: Although total RNA concentrations were very low in canine serum samples, 421 different miRNAs were detectable with sufficient signal intensity on the miRNA microarrays. About 30 miRNAs were differentially expressed in the two groups, but did not reach statistical significance. No significant differences were found using specific miRNA PCR assays. Conclusions: More than 400 miRNAs can be detected in canine serum samples. Changes in expression levels of various miRNAs between healthy and DCM dogs could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases Blood was drawn from two groups of Doberman Pinschers: 4 healthy dogs and 4 dogs suffering from dilated cardiomyopathy. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 8 serum samples were analyzed and the groups were compared
2013-03-22 | E-GEOD-36976 | biostudies-arrayexpress
Project description:To assess the effects of quantitative SOX9 dosage changes on gene expression in hESC-derived cranial neural crest cells, we performed genome editing of the H9 hESC lines to tag SOX9 with FKBPV36, V5, and mNeonGreen. Upon differentiating edited hESC to cranial neural crest cells using an established protocol, addition of differing concentrations of the degrader molecule dTAGV-1 results in different SOX9 concentrations, as measured by flow cytometry. We then profiled gene expression profiling in each of these SOX9 concentrations
2022-07-04 | GSE205902 | GEO
Project description:To assess the effects of quantitative SOX9 dosage changes on chromatin accessibility in hESC-derived cranial neural crest cells, we performed genome editing of the H9 hESC lines to tag SOX9 with FKBPV36, V5, and mNeonGreen. Upon differentiating edited hESC to cranial neural crest cells using an established protocol, addition of differing concentrations of the degrader molecule dTAGV-1 results in different SOX9 concentrations, as measured by flow cytometry. We then profiled chromatin accessibility in each of these SOX9 concentrations
2022-07-04 | GSE205900 | GEO
Project description:Conventional high-grade osteosarcoma is a primary malignant bone tumor, which is most prevalent in adolescence. Survival rates of osteosarcoma patients have not improved significantly in the last 25 years. Aiming to increase this survival rate, a variety of model systems are used to study osteosarcomagenesis and to test new therapeutic agents. Such model systems are typically generated from an osteosarcoma primary tumor, but undergo many changes due to culturing or interactions with a different host species, which may result into differences in gene expression between primary tumor cells, and tumor cells from the model system. We aimed to investigate whether gene expression profiles of osteosarcoma cell lines and xenografts are still comparable to those of the primary tumor. Osteosarcoma can be subdivided into several histological subtypes, of which osteoblastic, chondroblastic, and fibroblastic osteosarcoma are the most frequent ones. Using nearest shrunken centroids classification, we have generated an expression profile that can predict these histological subtypes in both osteosarcoma biopsies (n=66), as well as in two osteosarcoma model systems, i.e. osteosarcoma cell lines (n=13) and xenografts (n=18). Based on the preservation of mRNA expression profiles that are characteristic for the histological subtype we propose that these model systems are representative to the primary tumor from which they are derived. Genome-wide expression profiling was performed on pre-treatment diagnostic biopsies of 76 resectable high-grade osteosarcoma patients from the EuroBoNet consortium (www.eurobonet.eu). Samples with a main histological subtype (n=66) were selected for subsequent subtype analyses. Out of the EuroBoNeT panel of 19 cell lines, 13 cell lines were recorded to belong to a main histological subtype. This set of 13 cell lines contained 4 cell lines derived from fibroblastic, and 9 cell lines derived from osteoblastic osteosarcomas. The 13 osteosarcoma cell lines IOR/MOS, IOR/OS10, IOR/OS14, IOR/OS15, IOR/OS18, IOR/OS9, IOR/SARG, KPD, MG-63, MHM, OHS, OSA, and ZK-58 were maintained in RPMI 1640 (Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal calf serum and 1% Penicillin/Streptomycin (Invitrogen) as previously described (PMID: 19787792). The osteosarcoma xenograft model is described in Kresse et al. (PMID: 21713766) In short, human tumors were implanted directly from patient samples and successively passaged subcutaneously in nude mice. Eighteen different xenografts were used, of which 3 were derived from chondroblastic, and 15 from osteoblastic osteosarcomas. Osteosarcoma and xenograft tissue was handled as previously described in Buddingh, Kuijjer et al. (PMID: 21372215) Osteosarcoma cell lines were prepared as in Ottaviano et al. (PMID: 19787792) RNA isolation, synthesis of cDNA, cRNA amplification, and hybridization of cRNA onto the Illumina Human-6 v2.0 Expression BeadChips were performed as described in Buddingh, Kuijjer, et al. (PMID: 21372215) Microarray data processing and quality control were performed using the statistical language R as described in Buddingh, Kuijjer, et al. (PMID: 21372215) We performed a factorial LIMMA analysis comparing 50 osteoblastic, 9 chondroblastic, and 7 fibroblastic osteosarcomas pre-chemotherapy biopsies. Probes with Benjamini and Hochberg False discovery rate-adjusted P-values < 0.05 were considered to be significantly differentially expressed. The gene expression profile was generated on the dataset of biopsies using Bioconductor package PAMR. Internal cross-validation was performed 50 times. A threshold was selected where the error rate of the prediction profile was minimal. The minimum error rate was representative of 50 independent simulations. In order to minimize optimization bias, we validated the profile on an independent dataset of osteosarcoma biopsies (n=5), containing 1 chondroblastic osteosarcoma and 4 osteoblastic osteosarcomas. We subsequently applied the validated prediction profile to two independent datasets, the first consisting of gene expression data of osteosarcoma cell lines, the second of xenografts. Expression of the probes that composed the prediction profile was verified using a factorial LIMMA analysis, comparing chondroblastic, fibroblastic, and osteoblastic osteosarcoma biopsy samples.
2011-09-20 | E-GEOD-30699 | biostudies-arrayexpress