International Dental Journal, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Cancer Cell, Journal Year: 2023, Volume and Issue: 41(8), P. 1397 - 1406
Published: Aug. 1, 2023
The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 in 10 cohorts create cohesive powerful dataset scientific discovery. We outline efforts by the CPTAC working group harmonization, dissemination, computational resources aiding biological discoveries. also discuss challenges integration analysis, specifically unique of with both nucleotide sequencing mass spectrometry proteomics data.
Language: Английский
Citations
92
Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 4, 2025
Language: Английский
Citations
2
Blood, Journal Year: 2022, Volume and Issue: 140(13), P. 1533 - 1548
Published: July 27, 2022
Abstract We have developed a deep-scale proteome and phosphoproteome database from 44 representative acute myeloid leukemia (AML) patients the LAML TCGA dataset 6 healthy bone marrow–derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by proteomic data. identified examples posttranscriptionally regulated proteins both globally (ie, in all samples) also with recurrent driver mutations. For example, samples IDH1/2 mutations displayed elevated levels 2-oxoglutarate–dependent histone demethylases KDM4A/B/C, despite no changes messenger RNA for these genes; confirmed this finding vitro. In NPMc mutations, nuclear importins increased protein abundance showed that they interact but not wild-type NPM1. 2 cell surface (CD180 MRC1/CD206) expressed on blasts many (but CD34+ stem/progenitor cells) could represent novel targets immunologic therapies via flow cytometry. Finally, detected nearly 30 000 phosphosites samples; globally, were associated abnormal phosphorylation specific residues PTPN11, STAT3, AKT1, PRKCD. FLT3-TKD activating tyrosines cytoplasmic Src-family tyrosine kinases FGR HCK related signaling proteins. PML-RARA–initiated unique signature, TP53-mutant abundant serine-183 TP53 itself. This publicly available will serve as foundation further investigations dysregulation pathogenesis.
Language: Английский
Citations
63
PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(1), P. e1011851 - e1011851
Published: Jan. 30, 2024
The unique expression patterns of circRNAs linked to the advancement and prognosis cancer underscore their considerable potential as valuable biomarkers. Repurposing existing drugs for new indications can significantly reduce cost treatment. Computational prediction circRNA-cancer drug-cancer relationships is crucial precise therapy. However, prior computational methods fail analyze interaction between circRNAs, drugs, at systematic level. It essential propose a method that uncover more information achieving cancer-centered multi-association prediction. In this paper, we present novel method, AutoEdge-CCP, unveil cancer-associated drugs. We abstract complex into multi-source heterogeneous network. network, each molecule represented by two types information, one intrinsic attribute molecular features, other link explicitly modeled autoGNN, which searches from both intra-layer inter-layer message passing neural significant performance on multi-scenario applications case studies establishes AutoEdge-CCP potent promising association tool.
Language: Английский
Citations
15
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: July 7, 2024
Omics techniques generate comprehensive profiles of biomolecules in cells and tissues. However, a holistic understanding underlying systems requires joint analyses multiple data modalities. We present DPM, fusion method for integrating omics datasets using directionality significance estimates genes, transcripts, or proteins. DPM allows users to define how the input are expected interact directionally given experimental design biological relationships between datasets. prioritises genes pathways that change consistently across penalises those with inconsistent directionality. To demonstrate our approach, we characterise gene pathway regulation IDH-mutant gliomas by jointly analysing transcriptomic, proteomic, DNA methylation Directional integration survival information ovarian cancer reveals candidate biomarkers consistent prognostic signals transcript protein expression. is general adaptable framework prioritisation analysis multi-omics
Language: Английский
Citations
10
Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2392 - 2392
Published: July 23, 2024
Breast cancer is the second-leading cause of death among women in United States. Triple-negative breast (TNBC), a subtype cancer, an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which challenging to treat with standardized hormonal therapy. Kaempferol natural flavonoid antioxidant, anti-inflammatory, neuroprotective, anticancer effects. Besides anti-tumorigenic, antiproliferative, apoptotic effects, kaempferol protects non-cancerous cells. showed anti-breast effects by inducing DNA damage increasing caspase 3, 9, pAMT expression, modifying ROS production Nrf2 modulation, apoptosis cleaved PARP Bax downregulating Bcl-2 cell cycle arrest at G2/M phase; inhibiting immune evasion modulating JAK-STAT3 pathway; angiogenic metastatic potential tumors MMP-3 MMP-9 levels. holds promise for boosting efficacy agents, complementing their or reversing developed chemoresistance. Exploring novel TNBC molecular targets could elucidate its mechanisms identify strategies overcome limitations clinical application. This review summarizes latest research on kaempferol’s as anti-TNBC agent, highlighting promising but underexplored pathways delivery challenges warrant further investigation achieve successful translation.
Language: Английский
Citations
10
Cancers, Journal Year: 2022, Volume and Issue: 14(21), P. 5344 - 5344
Published: Oct. 29, 2022
SLC2A1 plays a pivotal role in cancer glycometabolism. has been proposed as putative driver gene various cancers. However, pan-cancer analysis of not yet performed. In this study, we explored the expression and prognosis across multiple databases. We conducted genetic alteration, epigenetic, functional enrichment analyses SLC2A. calculated correlation between tumor microenvironment using TCGA dataset. observed high levels with poor most The overall alteration frequency was 1.8% pan-cancer, promoter hypomethylation several Most m6A-methylation-related genes positively correlated 33 Moreover, mainly related to functions including epithelial–mesenchymal transition, glycolysis, hypoxia, cell-cycle regulation, DNA repair. Finally, associated neutrophils cancer-associated fibroblasts cancers significantly TMB MSI Notably, remarkably PD-L1 CTLA4 might serve an attractive biomarker for providing new insights into therapeutics.
Language: Английский
Citations
29
PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15019 - e15019
Published: March 17, 2023
Background Studies have shown that the expressions and working mechanisms of Dihydrolipoamide S-acetyltransferase (DLAT) in different cancers vary. It is necessary to analyze regulatory roles DLAT tumors systematically. Methods Online public-platform literature on relationships between expression levels tumor prognosis, methylation status, genetic alteration, drug sensitivity, immune infiltration has been reviewed. The includes such documents as Cancer Genome Atlas (TCGA), Human Protein (HPA), Tumor Immune Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis 2 (GEPIA2) Receiver Operating Characteristic plotter (ROC plotter). molecular were explored with Set Enrichment (GSEA). relationship down-regulated autophagy two liver hepatocellular carcinoma (LIHC) cell lines was confirmed western blot method, colony formation assay, transmission electron microscopy. Tissue microarrays validated through immunohistochemical staining DLAT. Results upregulated LIHC, lung adenocarcinoma (LUAD), squamous (LUSC), stomach (STAD) but head neck (HNSC) kidney renal clear (KIRC) comparison normal tissues. For LIHC patients treated 5-Fluorouracil Lenvatinib, those drug-resistant group are significantly high. In cells, will be inhibited, death induced when breaks down. Moreover, there exist positive correlations B DC Tregs, CD8+ T cells chromophobe (KICH), breast invasive (BRCA), prostate (PRAD), HPV+ HNSC. markers Tregs positively correlated Compared tissues, intensity amount marker CD49d increase. Conclusions Through this study, various cancer types can understood comprehensively. suggests may a prognostic for LUAD, LUSC, STAD KIRC. A high promote tumorigenesis by stimulating inhibiting anti-tumor immunity.
Language: Английский
Citations
21
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Sept. 13, 2023
Abstract Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics with whole genome sequencing across 1307 human tumors spanning various tissues to determine extent structural variant (SV) breakpoint patterns impact protein expression nearby genes. We find that about 25% hundreds genes SV-associated cis-regulatory alterations at mRNA level are similarly associated level. SVs enhancer hijacking, retrotransposon translocation, altered DNA methylation, or fusion transcripts implicated over-expression. combined levels considerably extend numbers patients somatically for critical pathways. catalog both SV involving patient survival breakpoints increased cell dependency cancer lines. Pan-cancer proteogenomics identifies targetable alterations, by virtue deregulated
Language: Английский
Citations
21
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)
Published: July 15, 2023
Abstract PLAGL2 is upregulated in various tumors, including bladder cancer (BCa). However, the mechanisms underlying tumorigenic effects of BCa remain unclear. In our study, we proved that was overexpressed tissues and correlated with decreased survival. Functionally, deficiency significantly suppressed proliferation metastasis cells vitro vivo. RNA sequencing, qRT‒PCR, immunoblotting, immunofluorescence staining, luciferase reporter, ChIP assays revealed disrupted Hippo pathway increased YAP1/TAZ activity by transactivating RACGAP1. Further investigations demonstrated activated signaling via RACGAP1-mediated RhoA activation. Importantly, inhibitor simvastatin or verteporfin abrogated proproliferative prometastatic enhanced PLAGL2. These findings suggest promotes progression RACGAP1/RhoA GTPase/YAP1 signaling. Hence, core nodes may be promising therapeutic targets for BCa.
Language: Английский
Citations
19