Protein expression changes in ovarian cancer during the transition from benign to malignant

TY - JOUR

T1 - Protein expression changes in ovarian cancer during the transition from benign to malignant

AU - Waldemarson, Sofia

AU - Krogh, Morten

AU - Alaiya, Ayodele

AU - Kirik, Ufuk

AU - Schedvins, Kjell

AU - Auer, Gert

AU - Hansson, Karin M

AU - Ossola, Reto

AU - Aebersold, Ruedi

AU - Lee, Hookeun

AU - Malmström, Johan

AU - James, Peter

PY - 2012/5/4

Y1 - 2012/5/4

N2 - 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.

AB - 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.

KW - 14-3-3 Proteins/metabolism

KW - Amino Acid Sequence

KW - Biomarkers, Tumor/analysis

KW - Female

KW - Humans

KW - Molecular Sequence Data

KW - Neoplasm Proteins/analysis

KW - Neoplasms, Glandular and Epithelial/metabolism

KW - Ovarian Neoplasms/metabolism

KW - Ovary/metabolism

KW - Phosphatidylinositol 3-Kinases/metabolism

KW - Proteome/analysis

KW - Proteomics/methods

KW - ROC Curve

KW - Sequence Analysis, Protein

KW - Signal Transduction

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods

KW - Tumor Cells, Cultured

U2 - 10.1021/pr201258q

DO - 10.1021/pr201258q

M3 - Journal article

C2 - 22471520

SN - 1535-3893

VL - 11

SP - 2876

EP - 2889

JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 5

ER -