Spatial and temporal tumour evolution and genetic biomarker discovery for personalised treatment in oesophageal adenocarcinoma

Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort

Biomedicines ◽

10.3390/biomedicines9111610 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1610

Author(s):

Jin Xu ◽

Rebecca Green ◽

Min Kim ◽

Jodie Lord ◽

Amera Ebshiana ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Metabolic Pathways ◽

Medical Information ◽

Biomarker Discovery ◽

Plasma Metabolites ◽

Csf Biomarkers ◽

Tryptophan Pathway ◽

Personalised Treatment ◽

Information Framework

Background: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites’ discriminatory performance in AD. Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046). Conclusions: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.

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NF1 may serve as a novel genetic biomarker of response to treatment and prognosis in glioblastoma (GBM).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14539 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14539-e14539

Author(s):

Bin Huang ◽

Ju Yang ◽

Kongcheng Wang ◽

Weitao Chen ◽

Hongbin Ni ◽

...

Keyword(s):

Biomarker Discovery ◽

Early Recurrence ◽

Response To Treatment ◽

Normal Brain ◽

Tumor Associated Macrophages ◽

Genome Wide ◽

A Genome ◽

Intrinsic Capacity ◽

The Relationship ◽

Genetic Biomarker

e14539 Background: The intrinsic capacity of glioblastoma (GBM) tumor cells to infiltrate normal brain predictably results in high rates of early recurrence. Little has changed over the last decade in the treatment available for GBM with survival remaining poor and a novel genetic biomarker is necessary found to predict response to treatment and prognosis in GBM. Methods: Biomarker discovery was performed by a genome-wide screen using DNA extracted from tissue and blood samples of GBM patients. The biomarker was then evaluated for its predictability in OS of GBM patients compared with the Chinese Glioma Genome Atlas (CGGA) and revealed the relationship with tumor-associated macrophages (TAMs). Results: Median OS for NF1-deleted/mutated GBM patients (n = 11) treated with surgery and Chemoradiotherapy was 9.1 mon vs 17.2 mon for NF1 wildtype ones(n = 47), HR (95% CI) 1.83 (0.8753,3.817), p = 0.1. In addition, NF1-deleted/mutated GBMs showed reduced tumor purity and more infiltration of tumor-associated macrophages through pathological stainings. Conclusions: These data suggest that NF1-deleted/mutated GBM patients have a poor prognosis and NF1 may play a role in organizing the tumor microenvironment. NF1 in GBM will be further evaluated in a planned randomized ph 2b study in newly diagnosed GBM patients.

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