Expression and Prognostic Value of Serum microRNA- 375 and microRNA- 182 in Correlation with Tissue Immunehistochemical Expression of Related Proteins, Serving as Novel Biomarkers in Colorectal Cancer

Document Type : Research Articles

Authors

1 Department of Clinical Chemistry, Theodor Bilharz Research Institute, Egypt.

2 Hepato-Gastroenterology Department, Theodor Bilharz Research Institute, Egypt.

3 Department of Pathology, Theodor Bilharz Research Institute, Egypt.

4 General Surgery Department, Theodor Bilharz Research Institute, Egypt.

Abstract

Background: Colorectal cancer (CRC) commonly evolves through precursor adenomatous polyps; however, reliable non-invasive biomarkers capable of distinguishing benign from malignant colorectal lesions remain limited. Circulating microRNAs have emerged as promising molecular indicators of tumour initiation and progression. Objectives: This study aimed to evaluate the diagnostic, prognostic, and mechanistic relevance of circulating miR-375 and miR-182 in patients with colorectal polyps and colorectal cancer. In addition, their performance was compared with conventional tumour markers and immunohistochemical staining of the tissues with caspase-3 was performed to assess apoptotic activity in malignant and adenomatous tissue. Methods: A total of 450 participants were enrolled, including 150 patients with CRC, 150 patients with colorectal polyps, and 150 healthy controls. Clinical, anthropometric, biochemical, histopathological, and immunohistochemical data were collected. Circulating miRNA-375 and miRNA-182 expression levels were quantified and correlated with clinicopathological parameters. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis, and logistic regression models were applied to identify independent predictors of CRC. Immunohistochemical staining for caspase-3 was performed on tissue samples. Results: miR-375 expression showed a progressive and significant downregulation from controls to polyps and CRC, whereas miR-182 demonstrated marked upregulation across the same spectrum (both p < 0.001). miR-375 and miR-182 exhibited excellent diagnostic performance for CRC detection. Logistic regression analysis identified miR-375 (OR = 0.003, p = 0.002) and miR-182 (OR = 8.254, p = 0.001) as independent predictors of CRC. Caspase positivity independently predicted lymph node metastasis (OR = 12.038, p = 0.004). miR-375 demonstrated significant inverse correlations with CEA and CA 19-9 levels. Conclusions: The reciprocal dysregulation of miR-375 and miR-182 reflects a molecular transition from benign colorectal polyps to invasive CRC. These circulating miRNAs exhibit superior diagnostic accuracy compared with conventional tumour markers and may represent valuable non-invasive tools for early detection and risk stratification of colorectal cancer.

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