Gene expression profile at single cell level of cells from OS tissue of OS lung metastatic patient
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE234187 | GEO | 2024/01/17
REPOSITORIES: GEO
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Project description:Osteosarcoma (OS) and Ewing’s sarcoma (EW) are the two most common pediatric solid tumors, after brain tumors. Multimodal treatments have significantly improved prognosis in localized disease but outcome is still poor in metastatic patients, for whom therapeutic options are often inadequate. Preclinical drug testing to identify promising treatment options that match the molecular make-up of these tumors is hampered by the lack of appropriate and molecularly well-characterized patient-derived models. To address this need, a panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected OS and EW tumors in NSG mice. Tumors were re-transplanted to next mice generations and fragments were collected for histopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least three passages. To evaluate the similarity of the model with primary tumor, we performed a global gene expression profiling and tissue microarrays (TMA), to assess tumor specific biomarkers on tissues from OS/EW tumors and their PDXs (1st and 3rd passage). Moreover, we verified the feasibility of these models for preclinical drug testing. We implanted 61 OS and 29 EW samples: 14/38 (37%) primary OS and 9/23 (39%) OS lung metastases successfully engrafted; while among EW, 5/26 (19%) primary samples and 1/3 (33%) metastases were established. Comparison between patient samples and PDXs, highlighted that histology and genetic characteristics of PDXs were stable and maintained over passages. In particular, correlative analysis between OS and EW samples and their PDXs was extremely high (Pearson’s r range r=0.94-0.96), while patient-derived primary cultures displayed reduced correlation with human samples (r=0.90-0.93), indicating that in vitro adaptation superimpose molecular alterations that create genetic diversion from original tumors. No significant differentially expressed gene profile was observed from the comparison between EW samples and PDXs (fold change > 2, adjusted p <0.05 at paired t-test). In OS, the comparison between OS patient-derived tumors and PDX indicated differences in 397 genes, mostly belonging to immune system functional category. This is in line with the idea that human immune cells are gradually replaced by murine counterparts upon engraftment in the mouse. As proof-of concept, two EW PDX and one OS PDX have been treated with conventional and innovated drugs to test their value in terms of drug-sensitivity prediction. Overall, our study indicated that PDX models maintained the histological and genetic markers of the tumor samples and represent reliable models to test sensitivity to novel drug associations.
2019-08-27 | E-MTAB-7568 | biostudies-arrayexpress
Project description:Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumor microenvironment (TME) for CRC remain elusive. Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.
2022-11-08 | GSE211576 | GEO
Project description:Tumor immune microenvironment difference primary and metastatic hepatocellular carcinoma
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Project description:Through an integrated transcriptome analysis of orthotopic colorectal cancer tumor-bearing mice and sham-operation mice, we showed the distinct immune microenvironment of pre-metastatic liver and identified MDSCs as the dominated cell type mediating pre-metastatic niche formation. MDSCs instead of other immune cell types were highly infiltrated in the pre-metastatic liver when compared with normal liver. Notably, immunosuppressive factors released by MDSCs such as HIF1α, iNOS, TGFβ were significantly up-regulated in the pre-metastatic liver. Increasing immune checkpoint molecules expression also reflected an immunosuppressive condition of pre-metastatic liver. The primary tumor may induce MDSCs accumulation via metabolic mechanism including glycolysis/gluconeogenesis, HIF-1 signaling pathway, and CCL28 chemokine axis. This study depicts the immune cell landscape of pre-metastatic cancer and primary CRC tumor, and provides insights into how MDSCs reshape the pre-metastatic niche facilitating circulating cancer cells colonization.
2020-04-30 | GSE147044 | GEO
Project description:Osteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung. We used gene chip-based global gene expression analysis of differential screening between parental Dunn and LM8 cells in order to reveal genes predominantly expressed in LM8 cells, which correlate with high metastatic potential. 2 cell lines
2011-03-04 | E-GEOD-26648 | biostudies-arrayexpress
Project description:Osteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung. We used gene chip-based global gene expression analysis of differential screening between parental Dunn and LM8 cells in order to reveal genes predominantly expressed in LM8 cells, which correlate with high metastatic potential.
2011-03-04 | GSE26648 | GEO
Project description:Burkholderia pseudomallei OS strain:OS Genome sequencing and assembly
| PRJNA188496 | ENA
Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS. In this study we analyzed two human metastatic OS cell lines and their parental non-metastatic lines. The two human metastatic OS cell line models were HOS/143B and SaOS-2/LM7. The HOS cell line, originally known as M.T. and later as TE-85, was derived from an OS of a 13 year-old girl. The 143B metastatic subline was generated from HOS by a Ki-RAS oncogene transformation [Rhim, J.S., et al., Characterization of human cells transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine. Int J Cancer, 1977. 19(4): p. 505-10.]. The SaOS-2 cell was derived from an OS of an 11 year-old girl, and its metastatic subline LM7, was developed by multiple in vivo selection of SaOS-2 cells in mice with pulmonary metastases [Jia, S.F., L.L. Worth, and E.S. Kleinerman, A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies. Clin Exp Metastasis, 1999. 17(6): p. 501-6.]. No replicates were included.
2012-04-24 | E-GEOD-37552 | biostudies-arrayexpress
Project description:Analysis of DNA methylation-based tumor immune microenvironment patterns in metastatic melanoma
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Project description:Analysis of two metastatic OS cell lines, KHOS and KRIB, and two non-metastatic OS cell lines, HOS and U2OS. Results show differences in gene expression between cell lines with different ability to metastasise in vivo.
2013-07-19 | GSE49003 | GEO