Circulating microRNAs and serum proteins in breast cancer patients: Diagnostic relevance and grade-specific expression patterns

doi:10.5493/wjem.v15.i3.108034

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World Journal of Experimental Medicine

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2220-315x

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Exp Med. Sep 20, 2025; 15(3): 108034
Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.108034

Circulating microRNAs and serum proteins in breast cancer patients: Diagnostic relevance and grade-specific expression patterns

Safinaz E El-Toukhy, Heba K Nabih, Mahmoud M Kamel, Hossam Elmasry, Sherien M El-Daly

Safinaz E El-Toukhy, Heba K Nabih, Sherien M El-Daly, Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Giza 12622, Egypt

Mahmoud M Kamel, Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo 11796, Egypt

Hossam Elmasry, Department of Laboratory, Baheya Centre for Early Detection and Treatment of Breast Cancer, Giza 12557, Egypt

Sherien M El-Daly, Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Giza 12622, Egypt

Author contributions: El-Toukhy SE was responsible for conceptualization, data curation, funding acquisition, and project administration; Nabih HK was responsible for formal analysis, investigation, and draft preparation; Kamel MM and Elmasry H were responsible for resources and data curation; El-Daly SM was responsible for conceptualization, formal analysis, writing-review and editing; All of the authors read and approved the final version of the manuscript to be published.

Supported by National Research Centre, Egypt, No. E120504.

Institutional review board statement: This study was performed in accordance with the principles of the Declaration of Helsinki. This study was reviewed and approved by the Ethical Committee of the National Research Centre, Egypt.

Informed consent statement: Informed consent was obtained from all participants to participate and publish the data.

Conflict-of-interest statement: The authors declare no conflicts of interest regarding the publication of this manuscript.

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: The authors confirm that the data supporting the findings of this study are available within the article.

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: Sherien M El-Daly, Professor, Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, 33 El Buhouth Street, Dokki, Giza 12622, Egypt. sm.el-daly@nrc.sci.eg

Received: April 3, 2025
Revised: May 10, 2025
Accepted: June 20, 2025
Published online: September 20, 2025
Processing time: 131 Days and 8.5 Hours

Abstract

BACKGROUND

Breast cancer is a prominent contributor to female cancer-related mortality. Early detection and accurate diagnosis are essential for effective management.

AIM

To evaluate the diagnostic relevance of a panel of circulating microRNAs (miRNAs) independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.

METHODS

In the present study, we analyzed the aberrant expression of miR-21, miR-221, miR-1246, miR-145, and miR-382, in addition to the tumor biomarkers cancer antigen 15-3 (CA15-3) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in breast cancer patients with varying grades.

RESULTS

Our results revealed distinct expression patterns of these miRNAs between grade II and III patients. Specifically, miR-21, miR-221, and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG were observed in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacy in differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggesting their interconnected roles in breast cancer progression. Receiver operating characteristic curve analysis demonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing the highest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancer grades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanced diagnostic accuracy and sensitivity.

CONCLUSION

These findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patients based on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting the development of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management of breast cancer patients.

Keywords: Breast cancer; Liquid biopsy; Tumor grading; MicroRNAs; Cancer antigen 15-3; 8-hydroxy-2′-deoxyguanosine; Sensitivity; Specificity

Core Tip: This study highlights the diagnostic utility of a panel of circulating microRNAs (miRNAs), miR-21, miR-221, miR-1246, miR-145, and miR-382, in stratifying breast cancer patients by tumor grade. Notably, miR-21 and miR-1246 exhibited the highest diagnostic power in distinguishing patients from healthy controls. Importantly, integrating these miRNAs with traditional protein biomarkers cancer antigen 15-3 and 8-hydroxy-2′-deoxyguanosine significantly enhanced diagnostic accuracy and sensitivity, underscoring the value of a multi-marker approach for non-invasive breast cancer detection and grading.