getPathFiedler2009: Serum peptidome profiling revealed platelet factor 4 as a...

In sgibb/MALDIquantExamples: Examples for MALDIquant

Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer

Description

This dataset contains 480 MALDI-TOF mass spectra used in Fiedler et al. 2009.

Usage

getPathFiedler2009

Format

A list containing 480 MassSpectrum-class objects.

Three sets:

1. 20 patients with pancreatic cancer and 20 healthy patients from University hospital Leipzig (set A, discovery).

2. 20 patients with pancreatic cancer and 20 healthy patients from University hospital Heidelberg (set B, discovery).

3. 20 patients with pancreatic cancer and 20 healthy patients from University hospital Leipzig (set C, validation, half resolution).

Set A and B were measured on the same target (batch). Set C was measured a few month later.
Each sample has four technical replicates.

Value

Returns a character vector of length two. The first element is the local path to the tar-archive of the spectra and the second is the path to the csv file with additional information about each spectrum.

Abstract

Purpose: Mass spectrometry-based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytic factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer-associated serum markers.

Experimental Design: For the discovery study, two sets of sera from patients with pancreatic cancer (n = 40) and healthy controls (n = 40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n = 20) and healthy controls (n = 20). Magnetic beads with different surface functionalities were used for peptidome fractionation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Data evaluation was carried out by comparing two different bioinformatic strategies. Following proteome database search, the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay.

Results: Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and a specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity, as shown by receiver operator characteristics curve analysis (AUROCcombined = 1.00). Mass spectrometry-based m/z 3884 peak identification and following immunologic quantitation revealed platelet factor 4 as the corresponding peptide.

Conclusions: MALDI-TOF MS-based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.

References

Fiedler, Georg Martin, et al. "Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer." Clinical Cancer Research 15.11 (2009): 3812-3819.

Examples

library("MALDIquantExamples")
getPathFiedler2009()

sgibb/MALDIquantExamples documentation built on Oct. 15, 2022, 3:25 a.m.