Serum protein profile at remission can accurately assess therapeutic outcomes and survival for serous ovarian cancer

Jinhua Wang; Ashok Sharma; Sharad A Ghamande; Stephen Bush; Daron Ferris; Wenbo Zhi; Mingfang He; Meiyao Wang; Xiaoxiao Wang; Eric Miller; Diane Hopkins; Michael Macfee; Ruili Guan; Jinhai Tang; Jin-Xiong She

doi:10.1371/journal.pone.0078393

Serum protein profile at remission can accurately assess therapeutic outcomes and survival for serous ovarian cancer

PLoS One. 2013 Nov 11;8(11):e78393. doi: 10.1371/journal.pone.0078393. eCollection 2013.

Authors

Jinhua Wang¹, Ashok Sharma, Sharad A Ghamande, Stephen Bush, Daron Ferris, Wenbo Zhi, Mingfang He, Meiyao Wang, Xiaoxiao Wang, Eric Miller, Diane Hopkins, Michael Macfee, Ruili Guan, Jinhai Tang, Jin-Xiong She

Affiliation

¹ Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, Augusta, Georgia, United States of America ; Sino-American Cancer Research Institute at Nanjing University of Technology and Jiangsu Cancer Hospital, Nanjing, Jiangsu province, China ; Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu, China ; Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, Jiangsu province, China.

Abstract

Background: Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer.

Experimental design: Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis.

Results: Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69-0.86) and more than 10 three-marker combinations have excellent AUC values (0.91-0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10(-3)).

Conclusion: We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / blood*
Blood Proteins / metabolism*
Disease-Free Survival
Female
Humans
Ovarian Neoplasms* / blood
Ovarian Neoplasms* / mortality
Ovarian Neoplasms* / therapy
Survival Rate

Substances

Biomarkers, Tumor
Blood Proteins

Grants and funding

This work was partly supported by a grant from the Georgia Cancer Coalition to DF and JXS. JXS was supported by the Georgia Research Alliance as an eminent scholar. JW was supported by Jiangsu Medical key Figure (RC2011091) and Jiangsu Government Scholarship and “333” Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.