ABSTRACT
Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.
Subject(s)
Colorectal Neoplasms/diagnosis , MicroRNAs/blood , Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenoma/blood , Adenoma/diagnosis , Adenoma/genetics , Adenoma/metabolism , Aged , Biomarkers, Tumor/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Early Diagnosis , Female , Gene Expression Regulation, Neoplastic , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , MicroRNAs/genetics , Middle Aged , Prognosis , Signal Transduction , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Micro-RNAs (miRs) are known to be differentially expressed in the serum of cancer patients and controls, and can thus be used as biomarkers for cancer screening. We detected the expression level of miR-29b-2, 155, 197 and 205 in the serum of female breast cancer patients and healthy controls to detect whether serum level of this chosen micro-RNAs could detect patients with breast cancer and also to detect difference in level of micro-RNAs between non-metastatic cases and metastatic cases, also we tried to detect any relation between level of micro-RNAs and the stage of the tumor, the size of tumor, nodal affection, the presence of metastasis and also the site of metastasis. Serum samples were collected from 130 female patients, 80 with non-metastatic breast cancer, 20 with metastatic breast cancer and 30 healthy controls. Real-time quantitative PCR was used to detect the expression level of miR-29b-2, -155, -197 and -205. The expression level of miR-29b-2, -155, -197 and -205 was significantly increased in the serum of breast cancer patients. miR-29b-2, -155, -197 and -205 may be useful as a blood-based biomarker for breast cancer screening.
