Advances in Proximal Fluid Proteomics for Disease Biomarker Discovery

Abstract

Although serum/plasma has been the preferred source for identification of disease biomarkers, these efforts have been met with little success, in large part due the relatively small number of highly abundant proteins that render the reliable detection of low abundant disease-related proteins challenging due to the expansive dynamic range of concentration of proteins in this sample. Proximal fluid, the fluid derived from the extracellular milieu of tissues, contains a large repertoire of shed and secreted proteins that are likely to be present at higher concentrations relative to plasma/serum. It is hypothesized that many, if not all, proximal fluid proteins exchange with peripheral circulation, which has provided significant motivation for utilizing proximal fluids as a primary sample source for protein biomarker discovery. The present review highlights recent advances in proximal fluid proteomics, including the various protocols utilized to harvest proximal fluids along with detailing the results from mass spectrometry- and antibody-based analyses.

Magnetically Promoted Rapid Immunoreactions Using Functionalized Fluorescent Magnetic Beads: A Proof of Principle

“…Eu(TTA) 3 (TOPO) 2 [thenoyltrifluoroacetylacetone (TTA) 3 ; tri-n-octylphosphine oxide (TOPO)] was prepared from europium(III) acetate hydrate (Sigma), TTA, and TOPO (13 ). Transmission electron microscope (TEM) images were measured by JEM-2010F (JEOL) at the Center for Advanced Material Analysis, Tokyo Institute of Technology.…”

“…A suspension of affinity magnetic beads with carboxylic acid (1.0 mg) was incubated with 10 mmol/L Eu(TTA) 3 (TOPO) 2 solution in acetone in the dark with vigorous shaking for 1 h at room temperature. Distilled water was added and acetone was evaporated under vacuum at 60°C.…”

“…Biomarkers provide information about disease progression and prognosis (1)(2)(3)(4). They are also widely used in the diagnosis of disease, often at the point of care.…”

Acute Phase Proteins as Cancer Biomarkers

“…In addition, other novel work in biomarker discovery involves proximal fluid proteomics. (Teng et al 2010) Proximal fluid, the fluid derived from the extracellular milieu of tissues, contains a large repertoire of shed and secreted proteins that are likely to be present at higher concentrations relative to plasma/serum. It has been hypothesized that many, if not all, proximal fluid proteins exchange with peripheral circulation, which has provided significant motivation for utilizing proximal fluids as a primary sample source for protein biomarker discovery.…”

Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction Obstruction

“…Urine is the proximal fluid of UPJO, as well as other urological diseases. Proximal fluids possess many potential advantages for revealing new pathology networks and insights into potential future biomarkers (4). In healthy individuals, urine obtained from the bladder is a combination of urine derived from both kidneys.…”