KRAS mutation and abnormal expression of Cripto-1 as two potential candidate biomarkers for detection of colorectal cancer development |
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Authors: | Somayeh Igder Javad Mohammadiasl Shima Azadpour Esrafil Mansouri Hassan Ashktorab Pooneh Mokarram |
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Institution: | 1. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;3. Faculty Member of Hematology Department, Abadan School of Medical Sciences, Abadan, Iran;4. Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;5. Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, District of Columbia;6. Colorectal Cancer Research Center, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran |
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Abstract: | Colorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto-1 (CR-1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty-five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR-1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR-1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR-1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR-1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development. |
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Keywords: | CR-1 abnormalities CRC CRC development G12D KRAS mutation |
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