Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 4 2025 12 25 248 254 Nina Lotfi Department of Biochemistry, Sha.C., Islamic Azad University, Shahrood, Iran Fatemeh Babajani Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. Seyed Askar Roghani Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Science, Kermanshah, Iran. Atefeh Kakavand Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. Mohammad Taghi Goodarzi Department of Biochemistry, Sha.C., Islamic Azad University, Shahrood, Iran Soheila Asadi Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. 2026 01 03 2026 01 04 Objectives: The genetic and environmental factors have crucial role in colorectal cancer (CRC) pathogenesis. Due to important role of proline , glutamic acid, and leucine-rich protein 1 (PELP1)    and c-Src genes in different types of malignancy, this study aimed to investigate the expression levels of the PELP1 and c-Src genes in tumor versus matched non-cancerous margin tissues of patients with CRC, and further evaluate their capacity as potential diagnostic biomarkers. Methods: The gene expression of PELP1 and c-Src in 31 tumor tissues and 31 non-cancerous margin tissues of CRC subjects was analyzed by the Real-Time PCR. Moreover, Receiver Operating Characteristic (ROC) curve analysis was utilized for the determination of these genes' RNA levels as potential biomarkers. Results: Our findings indicated the increased PELP1 (P=0.016) and c-Src (P=0.006) gene expression in tumor tissues, compared to non-cancerous margin tissues in CRC. The result of ROC analysis showed that the area under the curve (AUC)  for PELP1 and c-Src were 0.673 (Cut off:7.74, sensitivity:0.714, specificity:0.615) and 0.731 (Cut off:16.04, sensitivity: 0.857, specificity: 0.653), respectively. Conclusion: The higher expression of c-Src and PELP1 genes in tumor tissues compared to non-cancerous margin tissues indicated that these genes are critical components of the signaling pathways involved in CRC pathogenesis. Furthermore, the findings revealed that studied genes can have a potential for diagnosis purposes in CRC.  https://abi.tums.ac.ir/index.php/abi/article/view/176 https://abi.tums.ac.ir/index.php/abi/article/download/176/127