ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1640054
This article is part of the Research TopicAutoantibodies in Cancer: Diagnostic, Prognostic, and Therapeutic PotentialView all 3 articles
Five autoantibodies identified from immune complexes as breast cancer biomarkers
Provisionally accepted
- 1Department of Clinical Laboratory, Zhuhai Maternity and Child Health Hospital, Zhuhai, China
- 2Department of Clinical Laboratory, Zhuhai City People's Hospital, Zhuhai, China
- 3Department of breast surgery, Zhuhai Maternity and Child Health Hospital, Zhuhai, China
- 4Department of gynecology, Zhuhai Maternity and Child Health Hospital, Zhuhai, China
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Abstract Objective Comprehensive identification and profiling of antigens in serum immune complexes (ICs) is crucial for developing early diagnostic biomarkers for cancer. We therefore undertook this study to identify novel IC-derived autoantigens and autoantibodies in patients with breast cancer, and to evaluate their potential as new biomarkers. Methods ICs were purified from serum with C1q and Protein A/G affinity capture. The isolated complexes were digested with papain and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twelve candidate autoantibodies revealed by LC-MS/MS were first verified with a digital liquid chip method (DLCM) in baseline serum from 40 breast cancer patients and eight healthy controls. Five autoantibodies were then validated in independent cohorts of 33 breast cancer patients and 45 healthy controls, using DLCM. Results Autoantibodies targeting PF4, PSMB3, PRPF19, RTCB, SDHA, ENO1, PTBP2, PRDX6, ANP32A, VDAC1, MMP14 and HSPA4 were identified both purification methods. In the verification cohort, IgG autoantibodies against HSPA4, ENO1, PRDX6, PRPF19 and MMP14 were significantly increased in breast cancer patients with areas under the curve (AUCs) of 0.90, 0.89, 0.82, 0.78 and 0.77, respectively. Their combined panel discriminated breast cancer from controls with an AUC of 0.97. In the validation cohort, the same autoantibodies achieved AUCs of 0.79, 0.81, 0.73, 0.87, and 0.82, and the combination of these five autoantibodies yielded an AUC of 0.88. Conclusions The autoantibodies identified from ICs can serve as effective serum biomarkers for breast cancer. Anti-HSPA4, anti-PRPF19, anti-ENO1, anti-PRDX6, and anti-MMP14 autoantibodies showed significant increases in breast cancer patients. Keywords Complement 1q; immune complex analysis; autoantibodies; breast cancer
Keywords: Complement 1Q, immune complex analysis, Autoantibodies, breast cancer, digital liquid chip method
Received: 03 Jun 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Zheng, Li, Peng, Tang, Liang, Wang, Dai and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ningwei Zheng, Department of Clinical Laboratory, Zhuhai Maternity and Child Health Hospital, Zhuhai, China
Gongjun Tan, Department of Clinical Laboratory, Zhuhai Maternity and Child Health Hospital, Zhuhai, China
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