Prospective Procurement of Solid Tumor Tissue to Identify Novel Therapeutic Targets
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ABSTRACT:
PROVIDER: PRJNA298375 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR8496550_1.fastq.gz | Fastqsanger.gz | |||
| SRR8496550_2.fastq.gz | Fastqsanger.gz | |||
| SRR8496551_1.fastq.gz | Fastqsanger.gz | |||
| SRR8496551_2.fastq.gz | Fastqsanger.gz |
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Project description:Prospective Procurement of Solid Tumor Tissue to Identify Novel Therapeutic Targets
| PRJNA298376 | ENA
Project description:Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. We used microarray analysis to evaulate the effect of ischemia and tissue procurement conditions on the gene expression changes in renal cell carcinoma
2012-09-27 | GSE41137 | GEO
Project description:Background: Fatal cancer is often the result of spread, or metastasis, of a cancer cell from the site of its origin to a distant anatomic site. While the metastatic process and the foreign environment of the metastatic site impact a tumorâ??s biology, we continue to determine therapy for patients based upon their cancerâ??s site of origin. We have performed an unbiased analysis across metastatic solid tumors from common primary sites to determine the molecular impact of the metastatic process on site-specific biology and to identify novel therapeutic strategies. Methods: Global gene expression was used as a biological phenotype to perform a top-down analysis of 96 metastatic human tumors. Laser capture microdissection, RNA amplification, and microarray analysis were used to measure the transcription patterns of malignant epithelial cells. Genes, multi-gene expression â??signaturesâ??, and pathways associated with site of origin (SOO) and site of metastases (SOM) were identified using established computational approaches. SOO and SOM expression signatures were validated on multiple, independent datasets comprising 1217 samples (1104 samples from GSE2109 (Expression Project for Oncology) and 113 samples from GSE12630 (Monzon FA, Lyons-Weiler M, Buturovic LJ, Rigl CT et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol 2009 May 20;27(15):2503-8. PMID: 19332734). Reverse phase proteomics and in vitro tissue culture were used to validate associations between biological pathways, site of primary, and implicated therapeutic combinations. Findings: SOO has the dominant influence on solid tumor biology as samples segregate based upon their primary site during unsupervised hierarchical clustering. In addition, statistically significant associations are identified between single genes and pathways and each primary site investigated and SOO signatures for colon, breast, ovary, lung, and prostate cancers accurately identify primary site for independent samples of both local and metastatic tumors independent of degree of histological differentiation. The impact of SOM on tumor biology is evident as genes and pathways are significantly associated with metastatic site and SOM signatures can be generated but they are not strongly predictive when applied to localized tumors. Pathway analysis identified relatively increased expression of MYC, beta-catenin, and SRC gene sets in metastatic colorectal cancers which was confirmed with proteomic analysis of a sub-set of the original tumors. Within colorectal cancers, high SRC expression also correlates with predicted oxaliplatin sensitivity and the combination of an SRC inhibitor with oxaliplatin demonstrated synergy in three independent colorectal cancer cell lines. Interpretation: Our findings suggest that the complex alterations required for metastasis do not obscure the impact of a cancer cellâ??s origin. SOO signatures have the potential to be highly accurate diagnostic tools and the underlying site-specific biology can be used to identify novel therapeutic targets for advanced cancers. Keywords: Gene expression analysis Ninety-six laser capture microdissected adenocarcinoma patient tumor samples of various primary and metastatic sites were processed for Total RNA. Our 96-sample datatset was enriched by inclusion of previously deposited microarray data in GEO (reprocessed for this study): A total of 1217 samples (1104 samples from GSE2109, 113 samples from GSE12630) were reprocessed from the CEL files using RMA. Supplementary files: The reprocessed data matrices. A list of the 1217 Samples' GSM accession numbers and the corresponding reprocessed sample IDs.
2016-02-13 | E-GEOD-18549 | biostudies-arrayexpress
Project description:Background: Fatal cancer is often the result of spread, or metastasis, of a cancer cell from the site of its origin to a distant anatomic site. While the metastatic process and the foreign environment of the metastatic site impact a tumor’s biology, we continue to determine therapy for patients based upon their cancer’s site of origin. We have performed an unbiased analysis across metastatic solid tumors from common primary sites to determine the molecular impact of the metastatic process on site-specific biology and to identify novel therapeutic strategies. Methods: Global gene expression was used as a biological phenotype to perform a top-down analysis of 96 metastatic human tumors. Laser capture microdissection, RNA amplification, and microarray analysis were used to measure the transcription patterns of malignant epithelial cells. Genes, multi-gene expression “signatures”, and pathways associated with site of origin (SOO) and site of metastases (SOM) were identified using established computational approaches. SOO and SOM expression signatures were validated on multiple, independent datasets comprising 1217 samples (1104 samples from GSE2109 (Expression Project for Oncology) and 113 samples from GSE12630 (Monzon FA, Lyons-Weiler M, Buturovic LJ, Rigl CT et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol 2009 May 20;27(15):2503-8. PMID: 19332734). Reverse phase proteomics and in vitro tissue culture were used to validate associations between biological pathways, site of primary, and implicated therapeutic combinations. Findings: SOO has the dominant influence on solid tumor biology as samples segregate based upon their primary site during unsupervised hierarchical clustering. In addition, statistically significant associations are identified between single genes and pathways and each primary site investigated and SOO signatures for colon, breast, ovary, lung, and prostate cancers accurately identify primary site for independent samples of both local and metastatic tumors independent of degree of histological differentiation. The impact of SOM on tumor biology is evident as genes and pathways are significantly associated with metastatic site and SOM signatures can be generated but they are not strongly predictive when applied to localized tumors. Pathway analysis identified relatively increased expression of MYC, beta-catenin, and SRC gene sets in metastatic colorectal cancers which was confirmed with proteomic analysis of a sub-set of the original tumors. Within colorectal cancers, high SRC expression also correlates with predicted oxaliplatin sensitivity and the combination of an SRC inhibitor with oxaliplatin demonstrated synergy in three independent colorectal cancer cell lines. Interpretation: Our findings suggest that the complex alterations required for metastasis do not obscure the impact of a cancer cell’s origin. SOO signatures have the potential to be highly accurate diagnostic tools and the underlying site-specific biology can be used to identify novel therapeutic targets for advanced cancers. Keywords: Gene expression analysis
2016-02-13 | GSE18549 | GEO
Project description:An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies.
2021-12-07 | PXD030220 |
Project description:Therapeutic efficacy of INX-315, a selective CDK2 inhibitor, in solid tumors
| PRJNA1016438 | ENA
Project description:Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. We used microarray analysis to evaulate the effect of ischemia and tissue procurement conditions on the gene expression changes in renal cell carcinoma Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4C, 22C and 37C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was performed on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RIN index. Gene expression study was done on Affymetrix HG 133 Plus 2.0 Platform. Altered gene expression was assessed by paired, two-sample t-test between the zero time point and aliquots from various conditions obtained from the same tumor.
2012-09-27 | E-GEOD-41137 | biostudies-arrayexpress
Project description:Background: Inhibition of the interaction of the scaffold protein menin with the histone methyltransferase MLL1 (KMT2A) has recently emerged as a novel therapeutic strategy in different cancers. Purpose: Here we validate the proposed pathogenic function of the menin-MLL interaction in cancer with a novel probe inhibitor BAY-155. Methods: RNA-seq was used to investigate transcriptional effects of novel BAY-155 probe in thirteen cell lines from a range of solid tumor types. Results: Menin-MLL inhibition by BAY-155 in colorectal (SW1463, LoVo, DLD-1), prostate (22RV1, LNCaP, VCaP), pancreas (PANC-1, MiaPaCa2), breast (BT-474, ZR-75-1, MCF7), bladder (JMSU-1) and kidney (G401) tissue derived cancer cell lines resulted in moderate gene expression changes. Surprisingly, for the reported role of MLL1 as a co-activator of gene expression, inhibition by BAY-155 led predominantly to up-regulation of genes. We could not observe any evidences of an overarching, menin driven expression program, which is in contrast to previous reports for e.g. the Hox gene cluster. Conclusions: Our study adds important critical validation data to the menin-MLL interaction as therapeutic target in solid cancers. By using a more selective and potent inhibitor we propose that the potential therapeutic benefit of disrupting the menin-MLL interaction may be more restricted to specific cancers than previously predicted.
2020-02-27 | GSE136272 | GEO