Transcriptome sequencing of hepatocellular carcinoma biopsies (proteogenomic study)
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ABSTRACT:
PROVIDER: EGAS00001005074 | EGA |
REPOSITORIES: EGA
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Project description:We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies to define the deregulated pathways and heterogeneity among HCCs. We identified pathways that are differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. Integrative clustering identified HCC subgroups that show distinct regulation of biological processes, metabolic reprogramming and kinase activation.
| EGAS00001005073 | EGA
Project description:We report proteogenomic analysis of diffuse gastric cancers (GCs) in young population. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.
2018-12-06 | GSE122401 | GEO
Project description:Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, and is even more in women. EGFR mutations and ALK fusions are major alterations observed in NSLA. We have focused on NSLA without EGFR and ALK alteration (NENA) rather than NSLA with EGFR and ALK (EA). First, we selected 141 NSLA tissues, and performed proteogenomic analyses including the whole-genome sequencing (WGS), transcriptome, methylation EPIC array, total proteome and phosphoproteome. We then excluded 40 patients with EA and 7 patients with NENA microsatellite instability. Genome analysis revealed that TP53 (25%), KRAS (22%), ROS1 fusion (14%), and SETD2 (11%) were the most frequently mutated genes in NENA patients. Proteogenomic impact analysis revealed that STK11 and ERBB2 somatic mutations had broader effects on cancer-associated genes in NENA. Through DNA copy-number alteration analysis, we identified 22 prognostic proteins, influencing transcriptomic and proteomic changes. Gene set enrichment analysis revealed that the estrogen signaling emerged as the key pathway activated in NENA. A lot of proteogenomic evidence supported the increased estrogen signaling, such as copy-number deletions in chromosomes 14 and 21, STK11 mutation, and DNA hypomethylation of LLGL2 and ST14. Finally, saracatinib, an Src inhibitor, was suggested as a potential drug for targeting activated estrogen signaling in NENA, and was experimentally validated in vitro using cell line model. In this study, we enhanced our understanding of the etiology of NENA NSLA through the proteogenomic landscape, based on which we proposed saracatinib as an effective drug
2024-03-11 | GSE256092 | GEO
Project description:Background: Skeletal muscle myocytes have evolved into slow and fast-twitch types. These types are functionally distinct as a result of differential gene and protein expression. However, an understanding of the complexity of gene and protein variation between myofibers is unknown. Methods: We performed deep, whole cell, single cell RNA-seq on intact and fragments of skeletal myocytes from the mouse flexor digitorum brevis muscle. We compared the genomic expression data of 171 of these cells with two human proteomic datasets. The first was a spatial proteomics survey of mosaic patterns of protein expression utilizing the Human Protein Atlas (HPA) and the HPASubC tool. The second was a mass-spectrometry (MS) derived proteomic dataset of single human muscle fibers. Immunohistochemistry and RNA-ISH were used to understand variable expression. Results: scRNA-seq identified three distinct clusters of myocytes (a slow/fast 2A cluster and two fast 2X clusters). Utilizing 1,605 mosaic patterned proteins from visual proteomics, and 596 differentially expressed proteins by MS methods, we explore this fast 2X division. Only 36 genes/proteins were mosaic across all three studies, of which nine are newly described as variable between fast/slow twitch myofibers. An additional 414 genes/proteins were identified by two methods. Immunohistochemistry and RNA-ISH generally validated variable expression across methods presumably due to species-related differences. Conclusions: In this first integrated proteogenomic analysis of mature skeletal muscle myocytes we validate the main fiber types and greatly expand the known repertoire of twitch-type specific genes/proteins. We also demonstrate the importance of integrating genomic and proteomic datasets.
2020-01-15 | GSE143636 | GEO
Project description:Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, and is even more in women. EGFR mutations and ALK fusions are major alterations observed in NSLA. We have focused on NSLA without EGFR and ALK alteration (NENA) rather than NSLA with EGFR and ALK (EA). First, we selected 141 NSLA tissues, and performed proteogenomic analyses including the whole-genome sequencing (WGS), transcriptome, methylation EPIC array, total proteome and phosphoproteome. We then excluded 40 patients with EA and 7 patients with NENA microsatellite instability. Genome analysis revealed that TP53 (25%), KRAS (22%), ROS1 fusion (14%), and SETD2 (11%) were the most frequently mutated genes in NENA patients. Proteogenomic impact analysis revealed that STK11 and ERBB2 somatic mutations had broader effects on cancer-associated genes in NENA. Through DNA copy-number alteration analysis, we identified 22 prognostic proteins, influencing transcriptomic and proteomic changes. Gene set enrichment analysis revealed that the estrogen signaling emerged as the key pathway activated in NENA. A lot of proteogenomic evidence supported the increased estrogen signaling, such as copy-number deletions in chromosomes 14 and 21, STK11 mutation, and DNA hypomethylation of LLGL2 and ST14. Finally, saracatinib, an Src inhibitor, was suggested as a potential drug for targeting activated estrogen signaling in NENA, and was experimentally validated in vitro using cell line model. In this study, we enhanced our understanding of the etiology of NENA NSLA through the proteogenomic landscape, based on which we proposed saracatinib as an effective drug
2024-03-11 | GSE256091 | GEO
Project description:Proteogenomic Analysis of Medulloblastoma
| PRJNA430801 | ENA
Project description:CPTAC Proteogenomic Confirmatory Study
| PRJNA279694 | ENA
Project description:We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacentliver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related CC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct eatures in metabolic reprogramming, microenvironment dysregulation, cell roliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated ignaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and ell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.
| OEX001698 | NODE
Project description:We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacentliver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related CC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct eatures in metabolic reprogramming, microenvironment dysregulation, cell roliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated ignaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and ell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.
| OEX001909 | NODE
Project description:We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacentliver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related CC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct eatures in metabolic reprogramming, microenvironment dysregulation, cell roliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated ignaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and ell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.
| OEX001697 | NODE