Similar Datasets
Project description:Gene expression profiles at single cell level of murine undifferentiated pleomorphic sarcoma (UPS)
| PRJNA1119209 | ENA
Project description:Undifferentiated pleomorphic sarcomas (UPS) are thought to harbor a small population of cells with unique capability of tumor initiation and maintenance. These tumor initiating cells (TICs) are regarded as the drivers of cancer progression. However, the evidence for this tumor initiating cell (TIC) concept is based on the xenotransplantation assays in mice and the clinical relevance of the TIC concept remains unclear in UPS. We hypothesized that the distinct properties of the TICs would be reflected in the clinical outcome if the TIC concept is relevant in UPS. Here we performed global gene expression profiling of TIC-enriched side population (SP) fractions and non-SP fractions sorted from 15 UPS primary samples. Ninety-three genes were differentially expressed in between SP fractions and non-SP fractions. The UPS TIC gene expression signature score summarizing expression of these genes was calculated for a gene expression data and was correlated with clinical outcome. In the 15 samples used to generate the signature, patients with high scores in the SP fractions were associated with worse survival. We then tested the two independent published datasets with gene expression data on bulk unsorted samples, assuming that the TIC gene expression would persist in the non-TICs. Patients with high scores had significantly worse metastasis-free survival in both datasets. The significance of the score remained significant even considering for the known prognostic factor of UPS. Thus, gene expression signature derived from UPS TICs predicts clinical outcome, suggesting the clinical relevance of the TIC concept in UPS.
2016-02-01 | GSE55973 | GEO
Project description:To investigate the Setd1a function in the regulation of lung metastasis formation, we established mouse UPS cell lines in which each target gene has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq
2024-05-24 | GSE208363 | GEO
Project description:Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS. In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. In order to explore the molecular differences between UPS and LMS, We analyzed the expression data by SAMseq to identify the genes which were significantly differently expressed between UPS and LMS, between UPS and each LMS subtype.
2015-05-19 | E-GEOD-53844 | biostudies-arrayexpress
Project description:Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS.
2015-05-19 | GSE53844 | GEO
Project description:DNA methylation is frequently disrupted in sarcoma but little is known about the specific roles of DNA methyltransferases (DNMTs) in this process. Using an shRNA lentivirus-mediated genetic depletion approach, we found that reduction of DNMT3A or DNMT3B expression potently reduced UPS cell proliferation. Therefore, we performed RNA sequencing to identify global gene expression changes in DNMT3A- or DNMT3B-depleted cells.
2022-10-03 | GSE200026 | GEO
Project description:Although radiotherapy plays a crucial role in treating many cancers, the effect of radiation on tumor evolution remains unclear. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy. Most unirradiated UPS displayed initial linear evolution followed by subsequent branching evolution with distinct mutational processes during early and late development. Using metrics of genetic divergence between regions, we demonstrated evidence of strong selection pressures during UPS development that further increased during radiotherapy. We observed changes in subclone abundance following radiotherapy with subclone contraction tied to alterations in calcium signaling and demonstrated that inhibiting calcium transporters can radiosensitize sarcoma cells. Finally, ctDNA analysis accurately measured subclone abundance and enabled non-invasive monitoring of subclonal changes. These results demonstrate that radiation exerts selective pressures on UPS and suggest that targeting radioresistant subclonal populations could improve outcomes after radiotherapy.
2024-12-13 | GSE279683 | GEO
Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.
2009-03-24 | GSE13775 | GEO
Project description:Recent evidence suggests that immune checkpoint blockade (ICB) has some activity in metastatic dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS). We conducted a randomized, non-comparative phase 2 trial (NCT03307616) of nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n=17) and extremity/truncal UPS (n=10), with UPS patients receiving concurrent radiation therapy. The primary endpoint of pathologic response as assessed by percent hyalinization was observed to be a median of 8.8% in DDLPS patients and 89% in UPS patients and similar in nivolumab and ipilimumab/nivolumab arms in both cohorts . Higher intratumoral densities of T-regulatory cells were associated with absence of pathologic response (hyalinization<30%). Tumor infiltration by B-cells was associated with higher densities of T-regulatory cells before treatment; this association was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB with concurrent radiation may have significant efficacy in UPS and is associated complex immune changes in the tumor microenvironment in DDLPS and UPS.
2024-01-01 | GSE202361 | GEO
Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS. Genomic DNA was extracted from a total of 49 samples, 31 Undifferentiated pleomorphic Sarcomas and 18 Leiomyosarcomas. The DNA was labeled using Bioprime array CGH labeling kit (Invitrogen). Promega pooled male DNA was used as reference. Labeled DNA was hybridized onto BAC arrays containing ~32 000 BAC clones printed in singlets. BAC arrays were produced at the SWEGENE DNA Microarray Facility at Lund University.
2010-10-08 | E-GEOD-13775 | biostudies-arrayexpress