The Human Cell Surfaceome of Breast Tumors

Júlia Pinheiro Chagas Da Cunha,Anamaria Aranha Camargo,Sandro José De Souza,Lloyd J Old,Jorge Estefano Santana De Souza,Martin Pieprzyk,Pedro Alexandre Favoretto Galante,Dirce Maria Carraro

doi:10.1155/2013/976816

Abstract

Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors.

Highlights

Cell surface proteins are ideal targets for cancer therapy and diagnosis
Gene signatures identified by gene-expression profiling of breast tumors, such as the MammaPrint [4], which calculates a BioMed Research International prognostic score for node-negative patients at stage I or II based on the expression of a pool of 70 genes, contain more than 10% of trans-membrane (TM) proteins believed to be at the cell surface [5]
We further selected 573 cell surface genes as the most promising candidates for cancer diagnostics and therapy based on their expression profiling through the use of Massively Parallel Signature Sequencing (MPSS) and Serial Analysis of Gene Expression (SAGE) libraries

Summary

Introduction

Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. It has been shown that breast cancer is a very heterogeneous disease with four different molecular profiles based on the expression pattern of ERBB2, estrogen and progesterone receptors, and histological grade. These classes are associated with distinct clinical outcomes and responses to therapy [2]. According to the American Society of Clinical Oncology [3], breast cancers express some additional markers that have been shown to be useful in clinic: CA15-3, CA27.29, carcinoembryonic antigen (CEA), urokinase plasminogen activator, and plasminogen activator inhibitor 1, among others Several of these markers are cell surface transmembrane proteins, including ERBB2 and CEA. Gene signatures identified by gene-expression profiling of breast tumors, such as the MammaPrint [4], which calculates a BioMed Research International prognostic score for node-negative patients at stage I or II based on the expression of a pool of 70 genes, contain more than 10% of trans-membrane (TM) proteins believed to be at the cell surface [5]

Methods

Results

Conclusion