Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Sep 20, 2025; 15(3): 107711
Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.107711
Clinical significance of differential plasma proteins levels in the diagnosis of epithelial ovarian cancer
Noha H Ibrahim, Mona S Abdellateif, Dina S Serag, Ahmed Laymouna, Mennatallah S Elaguizy, Radwa Marawan Abdel Halim
Noha H Ibrahim, Dina S Serag, Department of Clinical Pathology, National Cancer Institute, Cairo 11796, Egypt
Mona S Abdellateif, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
Mona S Abdellateif, Department of Basic Medical Science, Galala University, Suez 15888, Egypt
Ahmed Laymouna, Department of Surgical Oncology, National Cancer Institute, Cairo 11796, Egypt
Mennatallah S Elaguizy, Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Radwa Marawan Abdel Halim, Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Author contributions: All authors contributed equally in the manuscript, read and approved the final version of the manuscript to be published.
Institutional review board statement: The study protocol was approved by the Institutional Review Board of the National Cancer Institute, Cairo University, which is in accordance with the 2013 declaration of Helsinki.
Informed consent statement: All recruited individuals signed an informed consent for participation in the study.
Conflict-of-interest statement: All authors declare that there is no possible conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at mona.sayed@nci.cu.edu.eg.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mona S Abdellateif, MD, PhD, Department of Cancer Biology, National Cancer Institute, Cairo University, 1 Fom Elkhaligue, Cairo 11796, Egypt. mona.sayed@nci.cu.edu.eg
Received: April 2, 2025
Revised: May 1, 2025
Accepted: June 24, 2025
Published online: September 20, 2025
Processing time: 135 Days and 20.8 Hours
Abstract
BACKGROUND

Ovarian cancer (OC) is the most lethal gynecological cancer among females, and its early diagnosis could help for better outcomes of the patients.

AIM

To investigate the utility of serum insulin-like growth factors-binding proteins 2 (IGFBP2), secreted phosphoprotein 1 (SPP1), thrombospondin 1 protein (TSP1) and D-dimer levels in addition to currently used biomarkers [cancer antigen 125 (CA125) and human epididymis protein 4 (HE4)] in the diagnosis of epithelial OC (EOC).

METHODS

This is a case-control study that included fifty females diagnosed with EOC, 10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute, and 30 healthy females as a control group. All subjects were assessed for serum HE4, CA125, IGFBP2, TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.

RESULTS

There was a statistically significant difference in serum levels between EOC, benign ovarian masses, and healthy control groups regarding CA125 and SPP1 (P < 0.001 for both markers), while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups (P < 0.001 for all markers) with no significant difference between EOC and benign ovarian masses groups. However, there was no statistically significant difference among EOC, benign ovarian masses, and healthy control groups regarding the TSP1 serum levels (P = 0.051). Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity, specificity, and area under curve of (93.3%, 100%, 0.968; respectively, P < 0.001).

CONCLUSION

SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses, while IGFBP2 can differentiate between healthy females and females with ovarian masses. Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.

Keywords: Ovarian cancer; Human epididymis protein 4; Cancer antigen 125; Insulin-like growth factors-binding proteins 2; Thrombospondin 1 protein; Secreted phosphoprotein 1; Biomarkers

Core Tip: Serum secreted phosphoprotein 1 (SPP1) can be a potential marker for the differentiation of patients with benign from those with malignant ovarian masses. insulin-like growth factors-binding proteins 2 (IGFBP2) and D-dimer could be potential markers for the diagnosis of patients with ovarian masses in relation to healthy controls. IGFBP2 could be a useful, sensitive diagnostic marker for epithelial ovarian cancer (EOC) patients. Also, combining SPP1 with cancer antigen 125 or thrombospondin 1 protein provides a high sensitivity (93.3%) and specificity (100%) for the detection of EOC patients.