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SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer

Authors Perumal J, Mahyuddin AP, Balasundaram G, Goh D, Fu CY, Kazakeviciute A, Dinish US, Choolani M, Olivo M

Received 26 August 2018

Accepted for publication 25 October 2018

Published 31 January 2019 Volume 2019:11 Pages 1115—1124


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li

Jayakumar Perumal,1,* Aniza Puteri Mahyuddin,2,* Ghayathri Balasundaram,1,* Douglas Goh,1 Chit Yaw Fu,1 Agne Kazakeviciute,1,3 US Dinish,1 Mahesh Choolani,2 Malini Olivo1

1Laboratory of Bio-optical Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore; 2Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3Department of Mathematics, Brunel University London, Uxbridge, UK

*These authors contributed equally to this work

Purpose: To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting.
Methods: SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections.
Results: Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity.
Conclusion: With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intraoperative EOC diagnostic test.
Keywords: surface-enhanced Raman spectroscopy, haptoglobin, epithelial ovarian cancer, ovarian cyst fluid, point-of-care diagnostics

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