Trends in cancer, Год журнала: 2024, Номер 10(9), С. 781 - 791
Опубликована: Июль 19, 2024
Язык: Английский
Cell, Год журнала: 2024, Номер 187(7), С. 1617 - 1635
Опубликована: Март 1, 2024
Язык: Английский
Процитировано
127
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Май 15, 2024
Abstract The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation potential observational genetic protein-cancer risk associations. We investigated associations 1463 plasma proteins with incidence 19 cancers 9 cancer subsites participants (average 12 years follow-up). Emerging were further explored using two approaches, cis -pQTL exome-wide scores (exGS). identify 618 associations, which 107 persist for cases diagnosed more than seven after blood draw, 29 associated analyses, four had support from long time-to-diagnosis ( > 7 years) both exGS analyses: CD74 TNFRSF1B NHL, ADAM8 leukemia, SFTPA2 lung cancer. present multiple including many detectable before diagnosis that concordant evidence suggesting a possible role development.
Язык: Английский
Процитировано
17
Journal of Proteome Research, Год журнала: 2024, Номер 23(2), С. 532 - 549
Опубликована: Янв. 17, 2024
Since 2010, the Human Proteome Project (HPP), flagship initiative of Organization (HUPO), has pursued two goals: (1) to credibly identify protein parts list and (2) make proteomics an integral part multiomics studies human health disease. The HPP relies on international collaboration, data sharing, standardized reanalysis MS sets by PeptideAtlas MassIVE-KB using Guidelines for quality assurance, integration curation non-MS neXtProt, plus extensive use antibody profiling carried out Protein Atlas. According neXtProt release 2023-04-18, expression now been detected (PE1) 18,397 19,778 predicted proteins coded in genome (93%). Of these PE1 proteins, 17,453 were with mass spectrometry (MS) accordance 944 a variety methods. number PE2, PE3, PE4 missing stands at 1381. Achieving unambiguous identification 93% encoded from across all chromosomes represents remarkable experimental progress list. Meanwhile, there are several categories that have proved resistant detection regardless protein-based methods used. Additionally some PE1–4 probably should be reclassified PE5, specifically 21 LINC entries ∼30 HERV entries; being addressed present year. Applying wide array biological clinical ensures other omics platforms as reported Biology Disease-driven teams pathology resource pillars. Current positioned transition its Grand Challenge focused determining primary function(s) every itself networks pathways within context
Язык: Английский
Процитировано
15
Journal of Proteome Research, Год журнала: 2024, Номер unknown
Опубликована: Окт. 31, 2024
Recent improvements in proteomics technologies have fundamentally altered our capacities to characterize human biology. There is an ever-growing interest using these novel methods for studying the circulating proteome, as blood offers accessible window into health. However, every methodological innovation and analytical progress calls reassessing existing approaches routines ensure that new data will add value greater biomedical research community avoid previous errors. As representatives of HUPO's Human Plasma Proteome Project (HPPP), we present 2024 survey current community, including latest build PeptideAtlas now comprises 4608 proteins detected 113 sets. We then discuss updates established methods, emerging technologies, investigations proteoforms, protein networks, extracellualr vesicles, antibodies microsamples. Finally, provide a prospective view tools studies proteins.
Язык: Английский
Процитировано
4
Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e009867 - e009867
Опубликована: Янв. 1, 2025
Background Concurrent KRAS LKB1 (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells. Methods Expression NK activating ligands in NSCLC line and patient data were analyzed. Cell surface expression MICA/B lines was determined flow cytometry while ligand shedding both blood ELISA. We engineered antibody-dependent cellular cytotoxicity (ADCC) enhanced monoclonal antibody, AHA-1031, which prevents without interfering with binding group 2D cancer cells via superior ADCC. performed vitro assays using ELISA cytometry-based confirm that our antibody potently binds stabilizes across other solid tumor lines. Additionally, we used two KL a patient-derived xenograft (PDX) model demonstrate vivo antitumor efficacy analysis for profiling. Results exhibit high secrete soluble vitro. Soluble is also detected samples. AHA-1031 the α3 domain MICA/B, preventing exhibits affinity specificity inducing ADCC Our effectively additional types demonstrates broad specificity. show models PDX model, treatment monotherapy significantly inhibits growth compared vehicle-treated animals no observable toxicity. Tumor tissues from treated mice increased infiltrates activated populations. Conclusions Activating stabilization offers potent therapy option tumors. are shed different tumors making this universally applicable.
Язык: Английский
Процитировано
0
Livers, Год журнала: 2025, Номер 5(1), С. 2 - 2
Опубликована: Янв. 14, 2025
Chronic liver disease poses significant challenges to healthcare systems, which frequently struggle meet the needs of end-stage patients. Early detection and management are essential because damage fibrosis potentially reversible. However, implementation population-wide screenings is hindered by asymptomatic nature early chronic disease, along with risks costs associated traditional diagnostics, such as biopsies. This study pioneers development innovative, minimally invasive methods capable improving outcomes patients identifying biomarkers using quantification translational potential. A targeted mass spectrometry assay based on stable isotope standard protein epitope signature tags (SIS-PrESTs) was employed for absolute 108 proteins in just two microliters plasma. The plasma profiles were derived from various stages etiologies, including healthy controls. set potential stratifying identified through differential expression analysis supervised machine learning. These findings offer promising alternatives improved diagnostics personalized treatment strategies management. Moreover, our approach fully compatible existing technologies that facilitate robust clinically relevant targets via disruptive sampling methods.
Язык: Английский
Процитировано
0
Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)
Опубликована: Янв. 15, 2025
Язык: Английский
Процитировано
0
Cell, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Clinical Proteomics, Год журнала: 2025, Номер 22(1)
Опубликована: Янв. 21, 2025
The standard "7 + 3" induction results in 30% of de novo acute myeloid leukemia (AML) patients not achieving complete remission (CR). We aimed to utilize the Olink® platform compare bone marrow plasma proteomic profiles newly diagnosed AML who did and achieve CR following treatment. This prospective study included 43 untreated patients, stratified into (n = 29) non-CR 14) groups based on their response therapy. employed Explore-384 Inflammation for analysis investigate differences protein levels between groups. Proteomic demonstrated that group exhibited significantly higher ARTN CCL23 than group. Immunohistochemical staining confirmed a proportion tissue samples with intense (25.40% vs. 7.05%, p 0.013) (24.14% 14.29%, 0.039) These findings were corroborated by bulk-RNA-seq, which indicated elevated mRNA expression (1.93 -0.09; 0.003) (1.50 0.12; 0.021) Human Protein Atlas provided external support our findings. suggest may serve as biomarkers predicting responsiveness AML. Using an enzyme-linked immunosorbent assay identify roles chemosensitivity enhance clinical applicability future.
Язык: Английский
Процитировано
0
Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101935 - 101935
Опубликована: Янв. 1, 2025
Chronic hepatic injury and inflammation from various causes can lead to fibrosis cirrhosis, potentially predisposing hepatocellular carcinoma. The molecular mechanisms underlying its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver plasma samples 330 individuals, including 40 healthy individuals 290 patients with histologically characterized due chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic disease. Our findings reveal dysregulated pathways related extracellular matrix, immune response, inflammation, metabolism in advanced fibrosis. We also identify 132 circulating proteins associated fibrosis, neurofascin growth differentiation factor 15 demonstrating superior predictive performance for fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared fibrosis-4 model (AUROC 0.85 CI 0.78-0.93]). These provide insights into pathogenesis highlight potential more accurate non-invasive diagnosis.
Язык: Английский
Процитировано
0