Single cell RNA-sequencing of undifferentiated pleomorphic sarcomas and leiomyosarcomas.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212527 | GEO | 2023/12/12
REPOSITORIES: GEO
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2024-09-30 | E-MTAB-13947 | biostudies-arrayexpress
Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Experiment Overall Design: Gene expression of 105 soft tissue tumor samples consisting of synovial sarcoma (n=16), myxoid liposarcoma (n=19), lipoma (n=3), well-differentiated liposarcoma (n=3), dedifferentiated liposarcoma (n=15), myxofibrosarcoma (n=15), leiomyosarcoma (n=6), malignant peripheral nerve sheath tumor (n=3), fibrosarcoma (n=4) and malignant fibrous histiocytoma (n=21) were analyzed using an Affymetrix HG-U133A array.
2008-11-22 | E-GEOD-6481 | biostudies-arrayexpress
Project description:Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exclusion is frequently used. In this study, array-based comparative genomic hybridization (array CGH) was used to analyze 20 UPS and 17 LMS samples from untreated patients. The LMS samples presented a lower frequency of genomic alterations compared with the UPS samples. The most frequently altered UPS regions involved gains at 20q13.33 and 7q22.1 and losses at 3p26.3. Gains at 8q24.3 and 19q13.12 and losses at 9p21.3 were frequently detected in the LMS samples. Of these regions, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 were significantly associated with reduced overall survival times in LMS patients. A multivariate analysis revealed that gains at 1q21.3 were an independent prognostic marker of shorter survival times in LMS patients (HR?=?13.76; P?=?0.019). Although the copy number profiles of the UPS and LMS samples could not be distinguished using unsupervised hierarchical clustering analysis, one of the three clusters presented cases associated with poor prognostic outcome (P?=?0.022). A relative copy number analysis for the ARNT, SLC27A3, and PBXIP1 genes was performed using quantitative real-time PCR in 11 LMS and 16 UPS samples. Gains at 1q21-q22 were observed in both tumor types, particularly in the UPS samples. These findings provide strong evidence for the existence of a genomic signature to predict poor outcome in a subset of UPS and LMS patients.
| S-EPMC3692486 | biostudies-literature
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
Project description:This study was performed to identify gene expression differences in not otherwise specified soft tissue sarcomas (NOS, malignant fibrous histiocytomas) and correlate them to histological findings and the clinical course. RNA was isolated and differential gene expression was analysed by the microarray technique. We used microarrays to detail the global gene expression differences between primary soft tissue sarcoma samples, harvested intraoperatively. Keywords: response to chemotherapeutic agent We compared the gene expression of ten different tumor samples of MFH/NOS sarcoma to determine global gene expression differences by microarray analysis.
2011-01-03 | E-GEOD-14325 | 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. 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