K-ras mutation gene affect the prognosis of colorectal cancer via the over-expression of ribonucleotide reductase M2

• Main Authors: Chiu-Chun Chang, 張秋純
• Other Authors: Chun-Che Lin
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/66vdu5

博士 === 中山醫學大學 === 醫學研究所 === 106 === Background: Colorectal cancer (CRC) ranks as the third-leading cause of cancer-related deaths in Taiwan. The expression of ribonucleotide reductase M2 (RRM2) and p53R2 is correlated with tumoral malignancy and progression in several types of cancer. Methods: The aim of this study was to determine the association of p53R2/RRM2 with upstream expression of miR-211 and the association of expression levels of p53, APC, and k-ras with clinical outcomes in CRC patients. The study consisted of 192 tumor tissue samples obtained from CRC patients. Immunohistochemistry and DNA direct sequencing were performed to analyze p53R2/RRM2 protein expression and p53/APC/k-ras gene mutations in these samples. The expression level of miR-211 was detected by the real-time polymerase chain reaction (PCR). Results: The results showed that the expression of p53R2 was lower and that of RRM2 was higher in patients with lymph node metastasis, distant metastasis, and late-stage CRC as compared to patients without lymph node metastasis, distant metastasis, and early-stage CRC. High expression of RRM2 in patients had a negative impact on overall survival (OS) and disease-free survival (DFS) in CRC. The expression of RRM2 in tumor tissues was positive and correlated with that of the k-ras gene mutation. Upstream miR-211 expression was negatively correlated with RRM2 expression in tumor tissues of CRC patients, and it was correlated with patient survival and tumoral recurrence in patients with k-ras mutations. Conclusion: We suggest that downregulation of miR-211 and overexpression of RRM2 in tumor tissues of CRC patients could be used to predict metastases and disease prognosis, especially in patients with k-ras gene mutations.