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Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

ABSTRACT: The high molecular heterogeneity of bladder tumours is responsible for significant variations in disease course, as well as elevated recurrence and progression rates, thereby hampering the introduction of more effective targeted therapeutics. The implementation of precision oncology settings supported by robust molecular models for individualization of patient management is warranted. This effort requires a comprehensive integration of large sets of panomics data that is yet to be fully achieved. Contributing to this goal, over 40 years of bladder cancer glycobiology have disclosed a plethora of cancer-specific glycans and glycoconjugates (glycoproteins, glycolipids, proteoglycans) accompanying disease progressions and dissemination. This review comprehensively addresses the main structural findings in the field and consequent biological and clinical implications. Given the cell surface and secreted nature of these molecules, we further discuss their potential for non-invasive detection and therapeutic development. Moreover, we highlight novel mass-spectrometry-based high-throughput analytical and bioinformatics tools to interrogate the glycome in the postgenomic era. Ultimately, we outline a roadmap to guide future developments in glycomics envisaging clinical implementation.

SUBMITTER: Azevedo R

PROVIDER: S-EPMC5710962 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

Azevedo Rita R Peixoto Andreia A Gaiteiro Cristiana C Fernandes Elisabete E Neves Manuel M Lima Luís L Santos Lúcio Lara LL Ferreira José Alexandre JA

Oncotarget 20170721 53

The high molecular heterogeneity of bladder tumours is responsible for significant variations in disease course, as well as elevated recurrence and progression rates, thereby hampering the introduction of more effective targeted therapeutics. The implementation of precision oncology settings supported by robust molecular models for individualization of patient management is warranted. This effort requires a comprehensive integration of large sets of panomics data that is yet to be fully achieved ...[more]

PMID: 29207682

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Project description:BackgroundDefining reliable brain markers for the prediction of abnormal behavioral outcomes remains an urgent but extremely challenging task in neuroscience research. This is particularly important for infant studies given the most dramatic brain and behavioral growth during infancy.MethodsIn this study, we proposed a novel prediction scheme through abstracting individual newborn's whole-brain functional connectivity pattern to three outlier measures (Triple O) and tested the hypothesis that neonates identified as "brain outliers" based on Triple O were more likely to develop as IQ outliers at 4 years of age. Without need for training with behavioral data, Triple O represents a novel proof-of-concept approach to predict later IQ outcomes based on neonatal brain data.ResultsTriple O correctly identified 42.1% true IQ outliers among a mixed cohort of 175 newborns with different term, twin, and maternal disorder statuses. Triple O also reached a high level of specificity (96.2%) and overall accuracy (90.3%). Further incorporating a demographic information indicator, the enhanced Triple O+ could further differentiate between high and low 4YR IQ outliers. Validation tests against seven independent reference samples revealed highly consistent results and a minimum sample size of ~50 for robust performance.ConclusionsConsidering that postnatal brain growth and various environmental factors likely also contribute to 4YR IQ, the fact that Triple O, based purely on neonatal functional connectivity data, could identify >40% of 4YR IQ outliers is striking. Together with the very high level of specificity, each outlier predicted by Triple O represents a meaningful risk but future efforts are needed to explore ways to identify the rest of outliers. Overall, with no need for training, a high level of robustness, and a minimal requirement on sample size, the proposed Triple O approach demonstrates great potential to predict later outlying IQ performances using neonatal functional connectivity data.

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Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

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Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

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