Combined Circulating miR-17-5p and Heat Shock Proteins as Diagnostic Biomarkers for Colorectal Cancer Progression

Document Type : Research Articles

Authors

1 Department of Molecular Biology, Faculty of Biotechnology, University of Sadat City, El-Sadat City, Egypt.

2 Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

3 Clinical Oncology Department, Faculty of Medicine, Suez University, Suez, Egypt.

4 Center for Converging Sciences and Emerging Technologies (CoSET), Benha National University (BNU), El-Obour City, P.O. 13518, Egypt.

Abstract

Objectives: Colorectal cancer (CRC) remains a significant global health challenge, and early diagnosis is essential for improving patient survival and treatment outcomes. Currently used serum biomarkers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), suffer from limited sensitivity and specificity, particularly in early-stage disease, which restricts their clinical utility. Therefore, identifying more reliable biomarkers for CRC detection and monitoring is urgently needed. This study investigated the diagnostic value of microRNA-17-5p (miR-17-5p) and selected heat shock proteins (HSPs) as potential non-invasive biomarkers for CRC. Methods: The study included patients with confirmed CRC, individuals with benign colorectal diseases, and healthy control subjects. Plasma levels of miR-17-5p and relative gene expression of HSPs were quantified in obtained samples using quantitative real-time PCR, while circulating HSP concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results: The results demonstrated a marked upregulation of miR-17-5p in CRC patients, showing a six-fold increase compared with healthy controls. Patients with benign colorectal disorders exhibited a moderate two-fold increase. Similarly, HSP40 and HSP90 expression levels were significantly elevated in CRC patients, whereas their levels were reduced in benign colorectal cases relative to healthy individuals. In contrast, HSP70 expression was significantly decreased in both CRC and benign colorectal patients compared with controls. Overall, miR-17-5p and HSPs showed superior diagnostic accuracy compared with conventional biomarkers. Notably, combined biomarker analysis significantly enhanced sensitivity and specificity in distinguishing CRC from benign colorectal conditions. Among the evaluated markers, miR-17-5p in combination with HSP40 and HSP90 demonstrated the strongest diagnostic performance. Conclusion: These findings suggest that this biomarker panel holds promise for CRC diagnosis, prognosis, and potential therapeutic targeting, offering improved strategies for clinical management.

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