SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]