Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies unique proteotypes associated with patient outcomes [WG-DASL]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA702554 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Non-small cell lung cancer (NSCLC) death rates exceed the next 3 prevalent cancers combined; however, most NSCLC tumors lack actionable mutations. Recent studies of NSCLC and other cancers revealed profound proteome remodelling with prognostic impact that is not fully predicted by DNA or RNA analyses. These revelations portend proteome-based cancer classification and treatment. This will require model systems that recapitulate tumor proteomes and phenotypes. A subset (~35%) of the most aggressive NSCLC can form a patient-derived xenograft (PDX). We generated 137 PDX models of aggressive NSCLC, which represent the histological, genome, transcriptome, and DNA methylation features and proteome remodelling of primary NSCLC. The models indicate 3 lung adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, candidate targets, and in adenocarcinoma, distinct stromal immune features. The PDX resource will foster proteome-directed stratification and development of new treatments for aggressive NSCLC.
2021-11-23 | GSE166998 | GEO
Project description:Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole-genome DASL (WG-DASL) assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We therefore assessed the utility of the WG-DASL assay in the analysis of peripheral whole blood gene expression profiles. We find that gene expression detection is significantly increased with the use of WG-DASL compared to the standard in vitro transcription-based direct hybridization (IVT), while globin-probe-negative WG-DASL did not exhibit significant improvements over globin-probe-positive WG-DASL. Globin reduction increases the detection sensitivity and reliability of both WG-DASL and IVT with little effect on raw intensity correlations: raw intensity correlations between total RNA and globin-reduced RNA were 0.970 for IVT and 0.981 for WG-DASL. Overall, the detection sensitivity of the WG-DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies.
2011-04-01 | GSE28064 | GEO
Project description:Cross-platform comparison between WG-DASL and IVT-based assays
2010-01-13 | GSE17575 | GEO
Project description:Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies unique proteotypes associated with patient outcomes
| PRJNA702550 | ENA
Project description:Thoracic patient-derived xenografts
| PRJNA339191 | ENA
Project description:Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies unique proteotypes associated with patient outcomes [HT12v4]
| PRJNA702553 | ENA
Project description:Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole-genome DASL (WG-DASL) assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We therefore assessed the utility of the WG-DASL assay in the analysis of peripheral whole blood gene expression profiles. We find that gene expression detection is significantly increased with the use of WG-DASL compared to the standard in vitro transcription-based direct hybridization (IVT), while globin-probe-negative WG-DASL did not exhibit significant improvements over globin-probe-positive WG-DASL. Globin reduction increases the detection sensitivity and reliability of both WG-DASL and IVT with little effect on raw intensity correlations: raw intensity correlations between total RNA and globin-reduced RNA were 0.970 for IVT and 0.981 for WG-DASL. Overall, the detection sensitivity of the WG-DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies. Peripheral whole blood samples were collected from eight human donors in PAXGene tubes. RNA was isolated after freezing and storage, and then prepared for gene expression analysis using the Illumina Human-Ref8 v3.0 BeadChip. Alpha and beta globin were reduced from a portion of the total RNA using the GLOBINclear assay (Ambion, Austin, TX, USA). Two methods of microarray target preparation were examined: Illumina IVT-based direct hybridization (IVT) and Illumina Whole-Genome DASL (WG-DASL). Two DASL Assay Oligo pools (DAP) were utilized for DASL target preparation: the DASL Assay Oligo Pool with globin probes (DAP +) and the DASL Asssay Oligo Pool without globin probes (DAP-).
2011-04-01 | E-GEOD-28064 | biostudies-arrayexpress
Project description:The use of Affymetrix U133 2.0 Plus chips on FFPE samples when coupled with a qPCR-based sample pre-assessment step, yielded satisfactory results from the point of view of biological reliability. When compared with the Illumina DASL WG platform, specifically designed for degraded RNA, the data generated with the Affymetrix platform showed a wider interquartile range (1.32 vs 0.57, p<2.2x10-16) suggesting a superior discriminatory power within samples as indicated by the good agreement with the immunohistiochemically derived ER status. FFPE primary breast cancer samples profiled using Illumina DASL WG platform after RNA amplification with the Nugen WT-Ovation FFPE System
2015-02-25 | GSE51451 | GEO
Project description:Non-small cell lung cancer (NSCLC) death rates exceed the next 3 prevalent cancers combined; however, most NSCLC tumors lack actionable mutations. Recent studies of NSCLC and other cancers revealed profound proteome remodelling with prognostic impact that is not fully predicted by DNA or RNA analyses. These revelations portend proteome-based cancer classification and treatment. This will require model systems that recapitulate tumor proteomes and phenotypes. A subset (~35%) of the most aggressive NSCLC can form a patient-derived xenograft (PDX). We generated 137 PDX models of aggressive NSCLC, which represent the histological, genome, transcriptome, and DNA methylation features and proteome remodelling of primary NSCLC. The models indicate 3 lung adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, candidate targets, and in adenocarcinoma, distinct stromal immune features. The PDX resource will foster proteome-directed stratification and development of new treatments for aggressive NSCLC.
2021-11-23 | GSE166997 | GEO
Project description:Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were “triple-negative” (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis. The study was designed to determine how stable patient-derived xenografts are across multiple transplant generations in mice, and to determine how closely xenografts established with pre-treatment samples cluster with xenografts established with post-treatment samples. Overall, pre-treatment and post-treatment samples derived from the same patient cluster together, and multiple transplant generations of xenografts derived from an individual patient cluster together.
2013-05-30 | E-GEOD-46106 | biostudies-arrayexpress