Protein Expression Changes
in Ovarian Cancer during
the Transition from Benign to Malignant
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Abstract
Epithelial ovarian carcinoma has in general a poor prognosis
since
the vast majority of tumors are genomically unstable and clinically
highly aggressive. This results in rapid progression of malignancy
potential while still asymptomatic and thus in late diagnosis. It
is therefore of critical importance to develop methods to diagnose
epithelial ovarian carcinoma at its earliest developmental stage,
that is, to differentiate between benign tissue and its early malignant
transformed counterparts. Here we present a shotgun quantitative proteomic
screen of benign and malignant epithelial ovarian tumors using iTRAQ
technology with LC–MALDI-TOF/TOF and LC–ESI-QTOF MS/MS.
Pathway analysis of the shotgun data pointed to the PI3K/Akt signaling
pathway as a significant discriminatory pathway. Selected candidate
proteins from the shotgun screen were further confirmed in 51 individual
tissue samples of normal, benign, borderline or malignant origin using
LC-MRM analysis. The MRM profile demonstrated significant differences
between the four groups separating the normal tissue samples from
all tumor groups as well as perfectly separating the benign and malignant
tumors with a ROC-area of 1. This work demonstrates the utility of
using a shotgun approach to filter out a signature of a few proteins
only that discriminates between the different sample groups