Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE208664 | GEO | 2022/09/13
REPOSITORIES: GEO
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Project description:Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of formalin-fixed paraffin embedded tumour specimens from 321 STS patients representing 11 histological subtypes.
2023-05-09 | PXD036226 | Pride
Project description:Canine soft tissue sarcomas were analyzed for gene expression changes following intratumoral treatment with collagen-anchored IL-2 and IL-12 therapy. Tumors were surgically resected at different intervals following treatment to assess persistence of any therapy-driven gene expression changes.
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Project description:To investigate and delineate differences in the transcriptomic profiles of canine soft tissue sarcoma types, we ran RNAseq on 29 tumor samples.
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Project description:NG2/CSPG4 is expressed in soft tissue sarcomas, however, its function in this tumor type, and its capacity to serve as a therapeutic target are unknown. Here, we used genetically engineered mice and cells from human tumors to determine the function of Ng2/Cspg4 in soft tissue sarcoma initiation and growth. We also investigated the potential for NG2/CSPG4 mAb immunotherapy to target human sarcomas established as xenografts in mice. Inhibiting Ng2/Cspg4 expression in established soft tissue sarcomas is associated with a smaller tumor volume and a reduction in cell proliferation. Intriguingly, deleting Ng2/Cspg4 at the time of tumor initiation has the opposite effect. Gene profiling found that Igfbp3/5 are substantially downregulated when Ng2/Cspg4 is depleted at the time of tumor initiation, but upregulated or only minimally downregulated when Ng2/Cspg4 is depleted after tumor initiation. Furthermore, the normal regulation of Igfbp is blunted when Ng2/Cspg4 is deleted at the time of tumor initiation. Our data show a difference in NG2/CSPG4 function in tumor initiation and maintenance, and provides pre-clinical evidence supporting NG2/CSPG4 as a therapeutic approach in soft tissue sarcoma.
2017-04-07 | GSE97489 | GEO
Project description:We hypothesize that there is a gene signature which will improve our ability to predict development of metastatic disease in STS patients. The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus non-metastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR confirmed increased relative expression of all five genes of interest in the metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible methods for comparing gene signatures in canine STSs. Further evaluation of differences in gene expression between metastatic and non-metastatic STSs is likely to identify genes important in the development of metastatic disease and improve our ability to prognosticate for individual patients.
2011-02-01 | GSE24601 | GEO
Project description:Background: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors has value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Methods: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. Results: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. Conclusions: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Extraploration of this downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human. Microarray expression dataset including STHS: Soft Tissue (localized) Histiocytic Sarcoma; VHS: Visceral (disseminated)Histiocytic Sarcoma; together with normal spleen (NS) samples. Comparisons were analysed in dyeswap on a 2-color platform against a common reference sample, consisting of a multitude of canine organs, including liver, spleen, kidney, lung, hart, intestine and bone.
2013-08-07 | E-GEOD-45832 | biostudies-arrayexpress
Project description:We hypothesize that there is a gene signature which will improve our ability to predict development of metastatic disease in STS patients. The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus non-metastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR confirmed increased relative expression of all five genes of interest in the metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible methods for comparing gene signatures in canine STSs. Further evaluation of differences in gene expression between metastatic and non-metastatic STSs is likely to identify genes important in the development of metastatic disease and improve our ability to prognosticate for individual patients. Comparison of metastatic and non-metastatic (defined as no metastasis for at least one year) untreated tumor biopsies.
2011-02-01 | E-GEOD-24601 | biostudies-arrayexpress
Project description:This study contains DNA and RNA sequencing data for various soft tissue sarcomas.
| EGAS00001006356 | EGA
Project description:Soft tissue sarcomas are aggressive mesenchymal cancers that affect more than 10,600 new patients per year in the US, about 40% of whom will die of their disease. Soft tissue sarcomas exhibit remarkable histologic diversity, with more than 50 recognized subtypes, but our knowledge of their genomic alterations is limited. Here we describe the results of an integrative analysis of DNA sequence, copy number, and mRNA expression in 207 samples encompassing seven major subtypes. Genes mutated in more than 5% of samples within a subtype were KIT (in gastrointestinal stromal cell tumors, or GISTs), TP53 (pleomorphic liposarcomas), PIK3CA (myxoid/round-cell liposarcoma), and NF1 (both myxofibrosarcoma and pleomorphic liposarcoma). We show evidence that PIK3CA mutations, found in 18% of myxoid/round-cell liposarcomas, activate AKT in vivo and are associated with poor outcomes. Point mutations in the tumor suppressor gene NF1 were discovered in both myxofibrosarcomas and pleomorphic liposarcomas, while genomic deletions were observed in all subtypes at varying frequencies. Finally, we found that short hairpin RNA-based knockdown of a subset of genes that are amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields the most detailed map of molecular alterations across diverse sarcoma subtypes to date and provides potential subtype-specific targets for therapy. Human soft tissue sarcoma samples and their matched normal DNA were profiled on Affymetrix 250K SNP (Sty) arrays per manufacturer's instructions
2010-07-05 | E-GEOD-21123 | biostudies-arrayexpress
Project description:SCX fractiond, TMT labeled pleomorphic soft-tissue sarcomas. 32 raw files (8x4) plus 8 pools (also TMT labeled) corresponding to each SCX fraction are submitted. The latter were used to propagate identifications across the runs.
2020-01-27 | PXD000617 | Pride