ABSTRACT
INTRODUCTION: Colorectal cancer (CRC) is a major health problem Worldwide, Egypt shows a high rate of early CRC in the world as 35% of 1,600 Egyptian CRC patients were under 40 with threefold increased risk of death within 5 years. DNA methylation-based biomarkers as methylated Septin9 (mSEPT9) has a promising role for detecting CRC. As well as set of nuclear matrix proteins associated with changes in the nuclear structure/architecture. detection of these nuclear proteins resulted in identification of biomarkers that are specific for colon cancer. Particular interest has been placed on colon cancer specific antigen-2(CCSA-2). METHODS: A total of 30 newly diagnosed CRC patients, 7 colonic adenoma patients, and 15 age- and sex-matched control subjects were recruited in this study. Plasma mSEPT9was assayed by Epi procolon kit, CCSA-2 by ELISA and, Occult blood in stool by Guaiac-based fecal occult blood test. The level of Colon Cancer mSEPT9 and CCSA-2 were carried on CRC patients both preoperatively and three months postoperatively. RESULTS: mSEPT9 has 96.7% sensitivity and 95.5% specificity in differentiating colorectal cancer patients from non-malignant cases. Also, our study showed a highly statistically significant difference between the pre and three months postoperative expression of mSEPT9 in colorectal cancer as there was a dramatically decrease in the expression of mSEPT9 postoperatively (p value < 0.001). The CCSA-2 at the cutoff level of >1.43 would provide 93.3% sensitivity and 90.9% specificity in differentiation between malignant and non-malignant cases. Also, the study showed that there is a statistically significant difference between colorectal cancer patients preoperatively and postoperatively according to CCSA-2 with dramatic decrease in its level postoperatively (p value > 0.001). CONCLUSION: The plasma SEPT9 DNA methylation level and Serum CCSA-2 could be used as promising non-invasive methods for observing the CRC patients postsurgical response to predict the occurrence of complete remission or relapses.
Subject(s)
Antigens, Neoplasm , Colorectal Neoplasms , Septins , Humans , Biomarkers, Tumor/genetics , Clinical Relevance , Colorectal Neoplasms/pathology , DNA Methylation , Early Detection of Cancer , Neoplasm Recurrence, Local/genetics , Septins/genetics , Antigens, Neoplasm/geneticsABSTRACT
BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers and leading causes of malignancy-related deaths all over the world. MicroRNAs (miRNAs) can regulate more than 60% of human genes, including tumor-stimulating, and -suppressor genes. Therefore, they can promote cancer development and affect risk of malignancy. miR-92a overexpression in CRC enhances tumor proliferation, invasion, and metastasis through downregulating different pro-apoptosis proteins including Bim. This study aimed to assess the role of plasma miR-92a as non-invasive marker in CRC patients, outline correlation between plasma miR-92a and serum Bim, and determine their correlations with clinicopathological parameters in CRC and adenoma patients. METHODS: A total of 54 newly diagnosed CRC patients, 15 colonic adenoma patients, and 15 age- and sex-matched control subjects were recruited in this study. Plasma miR-92a was assayed by TaqMan qRT-PCR and serum Bim was measured by ELISA. RESULTS: Statistically significant overexpression of serum miR-92a was observed in CRC patients as compared to adenoma and control groups (p<0.001 each) and lower serum Bim in CRC patients as compared to adenoma and control groups (p=0.001, p <0.001 respectively). The ROC curve analysis showed excellent AUC for plasma miR-92a in discriminating CRC from control (AUC=0.994), and adenoma (AUC=0.993) groups with highest diagnostic performance in discriminating CRC from controls (at cutoff 1.43, sensitivity 98.1%, specificity 93.9%), and adenoma patients (at cutoff 1.78, sensitivity 92.6%, specificity 93.3%). The diagnostic performance in discriminating early from late CRC was good (at cutoff 15, AUC=0.641, sensitivity 61.2%, specificity 80%). A significant negative correlation was evident between plasma miR-92a and serum Bim both in adenoma and CRC groups (P<0.001 for both). Higher plasma miR-92a expression (r=0.275, p=0.044) and lower serum Bim (r=-0.299, p=0.028) were found to be correlated with late CRC stages. CONCLUSION: Circulating miR-92a and Bim could be promising, non-invasive diagnostic and prognostic biomarkers in CRC.
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