62,606 research outputs found
Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer
PURPOSE:
Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers.
EXPERIMENTAL DESIGN:
Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples.
RESULTS:
We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting.
CONCLUSIONS AND CLINICAL RELEVANCE:
We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening
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DNA methylation-based classification of central nervous system tumours.
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology
A review of domain adaptation without target labels
Domain adaptation has become a prominent problem setting in machine learning
and related fields. This review asks the question: how can a classifier learn
from a source domain and generalize to a target domain? We present a
categorization of approaches, divided into, what we refer to as, sample-based,
feature-based and inference-based methods. Sample-based methods focus on
weighting individual observations during training based on their importance to
the target domain. Feature-based methods revolve around on mapping, projecting
and representing features such that a source classifier performs well on the
target domain and inference-based methods incorporate adaptation into the
parameter estimation procedure, for instance through constraints on the
optimization procedure. Additionally, we review a number of conditions that
allow for formulating bounds on the cross-domain generalization error. Our
categorization highlights recurring ideas and raises questions important to
further research.Comment: 20 pages, 5 figure
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