Creation of a Human Secretome: A Novel Composite Library of Human Secreted Proteins: Validation Using Ovarian Cancer Gene Expression Data and a Virtual Secretome Array

被引：72

作者：

Vathipadiekal, Vinod ^{[1
,2
]}

Wang, Victoria ^{[2
,3
]}

Wei, Wei ^{[1
,2
]}

Waldron, Levi ^{[2
,3
,4
]}

Drapkin, Ronny ^{[5
]}

Gillette, Michael ^{[1
,6
]}

Skates, Steven ^{[2
,7
]}

Birrer, Michael ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[4] CUNY, New York, NY 10021 USA

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Broad Inst MIT & Harvard, Cambridge, MA USA

[7] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA

来源：

CLINICAL CANCER RESEARCH | 2015年 / 21卷 / 21期

关键词：

MICROARRAY; BIOMARKER; IDENTIFICATION; TRANSMEMBRANE; SUBTRACTION; STATISTICS; DISCOVERY; CARCINOMA; SURVIVAL; ANTIGEN;

D O I：

10.1158/1078-0432.CCR-14-3173

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: To generate a comprehensive "Secretome" of proteins potentially found in the blood and derive a virtual Affymetrix array. To validate the utility of this database for the discovery of novel serum-based biomarkers using ovarian cancer transcriptomic data. Experimental Design: The secretome was constructed by aggregating the data from databases of known secreted proteins, transmembrane or membrane proteins, signal peptides, G-protein coupled receptors, or proteins existing in the extracellular region, and the virtual array was generated by mapping them to Affymetrix probeset identifiers. Whole-genome microarray data from ovarian cancer, normal ovarian surface epithelium, and fallopian tube epithelium were used to identify transcripts upregulated in ovarian cancer. Results: We established the secretome from eight public databases and a virtual array consisting of 16,521 Affymetrix U133 Plus 2.0 probesets. Using ovarian cancer transcriptomic data, we identified candidate blood-based biomarkers for ovarian cancer and performed bioinformatic validation by demonstrating rediscovery of known biomarkers including CA125 and HE4. Two novel top biomarkers (FGF18 and GPR172A) were validated in serum samples from an independent patient cohort. Conclusions: We present the secretome, comprising the most comprehensive resource available for protein products that are potentially found in the blood. The associated virtual array can be used to translate gene-expression data into cancer biomarker discovery. A list of blood-based biomarkers for ovarian cancer detection is reported and includes CA125 and HE4. FGF18 and GPR172A were identified and validated by ELISA as being differentially expressed in the serum of ovarian cancer patients compared with controls. (C) 2015 AACR.

引用

页码：4960 / 4969

页数：10

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