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Background/Aims: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. Methods: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. Results: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). Conclusion: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients. [ABSTRACT FROM AUTHOR]