Background: Colorectal cancer (CRC) is the third most common type of cancer, it is considered a genetically heterogeneous disease with different molecular pathways being involved in its initiation and progression. Testes-specific protease 50 (TSP50) gene is a member of cancer/testis antigens that encodes for threonine protease enzyme. Overexpression of TSP50 was found to enhance the progression and invasion of breast cancer and other malignant tumors. SERCA2 is widely expressed in several body tissues; its aberrant expression has been involved in many cancers. IL-8 is an inflammatory cytokine. Alongside its role in inflammation, its expression was reported to induce the migration of tumor cells.Aim: Study the expression of TSP50, SERCA2 and IL-8 in colorectal adenoma (CRA), CRC and normal colonic tissues to compare the expression of these biomarkers in relation to clinicopathological parameters and prognostic factors.Results: TSP50, SERCA2 and IL-8 expression varied between normal colonic tissues, CRA and CRC. Significant statistical association was detected between the three biomarkers’ overexpression and degree of dysplasia in CRA. Also, significant statistical relation was found between the three biomarkers’ overexpression and presence of lympho-vascular invasion, advanced TNM staging and high intra-tumoral inflammatory infiltrate. Multivariable analysis showed that the overexpression of the three biomarkers is significantly associated with worse prognosis.Conclusion: The expression of TSP50, SERCA2 and IL-8 was different between the normal tissue and neoplastic colorectal tissue on one hand and between CRA and CRC on the other. Increased expression of these biomarkers in neoplastic epithelial cells of colorectal carcinoma is associated with adverse prognostic factors and could be considered as independent prognostic factors.

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