Redefined complement C3c structures have significant increase in the plasma of ovarian cancer patients

Sep 29, 2026

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Ovarian cancer is a major gynecological malignancy with an urgent need for effective biomarkers. A study was designed to test whether plasma proteolytic products could serve as candidates, using a workflow combining CyDye labeling, macroporous reversed-phase liquid chromatography, reducing/nonreducing SDS-PAGE, and fluorescence imaging. Protease-based digests were analyzed by LC-MS/MS. The complement C3 derivative complement C3c showed disease-exclusive detection, with elevated levels linked to occurrence and progression, supporting proteolysis during complement deactivation as a mechanistic contributor.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Complement activation and C3 processing

Rationale for a proteolysis-based biomarker platform

J Chin MedAssoc Original article Redefined complement C3c structures have significant increase in the plasma of ovarian cancer patients Dong-Hao Chena, Yi-Wen Changa, Chin-Hsiang Chienb, Pao-Ling Torngc, Yeou-Guang Tsaya,d,* aProgram in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC; bOncoLock Co., LTD, Taipei, Taiwan, ROC; cDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan, ROC; dInstitute of Biochemistry and Molecular Biology, College of Life Science, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC Abstract Background: Ovarian cancer (OC) is the third most common gynecological cancer. Effective biomarkers are required for OC as in the case of other cancers. Therefore, here we explored whether plasma proteolytic products could serve as potential biomarkers. Methods: We devised a platform that incorporates CyDye labeling, macroporous reversed-phase liquid chromatography, reducing/ nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAG) , and fluorescence imaging. Paired preoperative and postoperative plasma samples from four patients were used to screen for possible proteolytic changes. For identified difference proteins, liquid chromatography-tandem mass spectrometry was used to analyze the protein digests using various proteases. Plasma samples from 33 healthy controls and 85 patients with OC were examined using an enzyme-linked immunosorbent assay. Results: Our analyses revealed that the circulating complement C3 derivative was present only in the diseased state. This 145-kDa species, under nonreducing conditions, could split into 72- , 39- , and 29-kDa fragments upon reduction, reminiscent of the C3c structure. While confirming the C3c identity, mass spectrometric analyses showed multiple C-terminal ends in the C3c α’1 fragment, which were utilized differently among patients with OC. Various ends were also observed in serum samples prepared using different complement activators, thus redefining C3c as a mixture of multiple molecular entities. Enzyme-linked immunosorbent assay (ELISA) targeting only canonical C3c demonstrated a strong correlation between increased plasma levels and the occurrence and progression of OC. Conclusion: Our findings suggest that plasma proteolysis during complement deactivation is explicitly involved in ovarian tumorigenesis and the associated protein changes may aid in developing next-generation cancer biomarkers. Keywords: Biomarkers; Complement C3; Mass spectrometry; Ovarian neoplasms; Proteolysis 568 [www.ejcma.org](www.ejcma.org)[ ](www.ejcma.org) Original Article. (2025) 88:7 J Chin MedAssoc Lay Summary: Ovarian cancer is a serious disease that affects many women worldwide, but early detection can significantly improve survival rates. In this study, researchers analyzed blood samples to identify biomarkers that could signal the presence of ovarian cancer. They developed an innovative method to compare blood samples taken from patients before and after surgery and identified a unique protein form known as complement C3c. This specific form was found exclusively in the blood of women with ovarian cancer. Complement C3c consists of distinct fragments, and its presence may reflect underlying mechanisms of cancer progression. Using a straightforward blood test, the scientists confirmed that elevated levels of this protein variant were strongly associated with both the presence and the stage of ovarian cancer. This breakthrough could pave the way for improved diagnostic blood tests, enabling earlier detection, faster intervention, and ultimately offering women a better chance at successful treatment and recovery. 1. INTRODUCTION Ovarian cancer (OC) is the third most common type of gynecological cancer and is characterized by poor prognosis and high mortality rates.1,2 The treatment of OC is often del

FAQs

What biomarker did the study focus on for ovarian cancer?

The study focused on a complement C3 derivative form known as complement C3c, assessed in plasma to detect ovarian cancer–associated changes.

How did researchers identify and characterize the complement C3c-related protein fragments?

They used an analytical platform combining CyDye labeling, macroporous reversed-phase liquid chromatography, reducing/nonreducing SDS-PAGE with fluorescence imaging, and LC-MS/MS to analyze digests from identified difference proteins.

What did the study find about complement C3c levels in patients?

Complement C3c was detected only in the diseased state, and ELISA measurements targeting canonical C3c showed strong correlations between increased plasma levels and ovarian cancer occurrence and progression.

Sep 29, 2026

Uploaded by Jiven