Causal association of immune cell phenotypes with osteosarcoma and the mediation role of blood metabolites: A two-steps, two-samples Mendelian randomization study DOI Creative Commons

Chicheng Niu,

Qingyuan Xu,

Weiwei Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Abstract Background: Immunogenic nature of osteosarcoma is well-established, but the precise roles immune cells and potential influence blood metabolites on its advancement remain unclear. Methods: Two-step, two-sample Mendelian randomization (MR) strategy was employed to investigate causal relation between risk cell distribution, we sought uncover measure mediating role metabolites. Our analysis incorporated a diverse range MR estimation techniques, encompassing inverse variance weighting (IVW), MR-Egger regression, weighted median, mode, simple mode. Additionally, conducted sensitivity analyses assess reliability our results. Results: revealed that three phenotypes exhibited positive with (CX3CR1 CD14- CD16-, CD25 CD45RA- CD4 not Treg, CD45 HLA DR+ CD8br), while four illustrated negative (BAFF-R IgD+ CD38- unsw mem, CD20 IgD- CD38-, Naive CD4+ %T cell, CD28+ CD45RA+ CD8br %CD8br). Moreover, mediation demonstrated effect CX3CR1 CD16- within monocyte panel (Total IVW: OR = 0.3330) predominantly mediated by dimethyl sulfone (0.0288, constituting 8.70% Total effect) unidentified metabolite X-12680 (0.0524, 15.74% effect). Conclusions: This investigation unveiled link osteosarcoma, potentially

Language: Английский

Machine learning-based analysis of genomic and transcriptomic data unveils sarcoma clusters with superlative prognostic and predictive value DOI Creative Commons
Miguel Esperança‐Martins,

Hugo Vasques,

Manuel Sokolov Ravasqueira

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Abstract Soft tissue sarcomas (STS) histopathological classification system has several conceptual caveats, impacting prognostication and treatment. The clinical molecular-based tools currently employed to estimate prognosis also have limitations. Clinically driven molecular profiling studies may cover these gaps. We performed DNA sequencing (DNAseq) RNA (RNAseq), portraying the profile of 102 samples 3 most common STS subtypes. RNAseq data was analyzed using unsupervised machine learning models, unravelling previously unknown patterns identifying 4 well-defined transcriptomic clusters. These clusters a clear prognostic value, finding that externally validated. This cluster-based classification’s value is superior accuracy used clinical-based (SARCULATOR nomograms) (CINSARC) tools. analysis DNAseq from same cohort revealed plethora unique and, in some cases, never documented targets for precision treatment across different

Language: Английский

Citations

0
Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities DOI Creative Commons

Ariane Lozac’hmeur,

Tyler Danek,

Qidi Yang

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Aug. 5, 2024

To enable interrogation of tumor HLA LOH as a clinical diagnostic for precision oncology, we developed and validated an assay that detects within the context FDA-approved test, Tempus xT CDx. Validation was conducted via: (1) analytical evaluation 17 archival patient samples 42 cell line admixtures (2) independent prevalence in HLA-A gene (HLA-A LOH) across 10,982 patients. evaluate prognostic relevance assessed 256 immunotherapy-treated non-small lung cancer (NSCLC) determine feasibility prospectively identifying enrolling patients into trial, established BASECAMP-1 (NCT04981119). We observed positive predictive agreement 97% negative 100% with ≥ 40% purity. 16.1% (1771/10,982), comparable to previous reports. associated longer survival among NSCLC adenocarcinoma (HR = 0.60, 95% CI [0.37, 0.96], p 0.032) trend towards shorter squamous 1.64, [0.80, 3.41], 0.183). In 20 months, screened 1720 subjects using AWARE program, 26 HLA-A*02 at 8 sites, 14 (54%) enrolled BASECAMP-1. conclusion, investigational enabling utilization diagnostic, prognostic, therapeutic applications.

Language: Английский

Citations

3
Mechanisms of Low MHC I Expression and Strategies for Targeting MHC I with Small Molecules in Cancer Immunotherapy DOI Creative Commons

S. W. Kong,

Jie Zhang, Longsheng Wang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 611, P. 217432 - 217432

Published: Dec. 25, 2024

Language: Английский

Citations

2
Precision cancer medicine platform trials: Concepts and design of AcSé-ESMART DOI
Birgit Geoerger, Francisco Bautista, Nicolás André

et al.

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 208, P. 114201 - 114201

Published: July 14, 2024

Language: Английский

Citations

1
Causal association of immune cell phenotypes with osteosarcoma and the mediation role of blood metabolites: A two-steps, two-samples Mendelian randomization study DOI Creative Commons

Chicheng Niu,

Qingyuan Xu,

Weiwei Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Abstract Background: Immunogenic nature of osteosarcoma is well-established, but the precise roles immune cells and potential influence blood metabolites on its advancement remain unclear. Methods: Two-step, two-sample Mendelian randomization (MR) strategy was employed to investigate causal relation between risk cell distribution, we sought uncover measure mediating role metabolites. Our analysis incorporated a diverse range MR estimation techniques, encompassing inverse variance weighting (IVW), MR-Egger regression, weighted median, mode, simple mode. Additionally, conducted sensitivity analyses assess reliability our results. Results: revealed that three phenotypes exhibited positive with (CX3CR1 CD14- CD16-, CD25 CD45RA- CD4 not Treg, CD45 HLA DR+ CD8br), while four illustrated negative (BAFF-R IgD+ CD38- unsw mem, CD20 IgD- CD38-, Naive CD4+ %T cell, CD28+ CD45RA+ CD8br %CD8br). Moreover, mediation demonstrated effect CX3CR1 CD16- within monocyte panel (Total IVW: OR = 0.3330) predominantly mediated by dimethyl sulfone (0.0288, constituting 8.70% Total effect) unidentified metabolite X-12680 (0.0524, 15.74% effect). Conclusions: This investigation unveiled link osteosarcoma, potentially

Language: Английский

Citations

0