大腸直腸癌K-ras突變基因影響臨床預後之機轉研究

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大肠直肠癌K-ras突变基因影响临床预後之机转研究

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

张秋纯 , 博士　　导师：林俊哲　　

繁体中文

核醣核苷酸还原酶亚基RRM2 ；微型核醣核酸miR-211 ；大肠直肠癌；复发； RRM2 ； miR-211 ； metastasis ； colorectal cancer

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摘要 │ 参考文献 (130) │ 国际计量

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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.

参考文献 ( 130 ) 〈TOP〉

3. 欧吉性、余方荣、许文鸿、王圣雯、吴登强、胡晃鸣。2012。大肠直肠癌的筛检与监测及台湾施行现况。台湾医界 55( 3):124-127。
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5. Andersen SN, Lovig T, Breivik J, Lund E, Gaudernack G, Meling GI, Rognum TO. K-ras mutations and prognosis in large-bowel carcinomas. Scand J Gastroenterol 32: 62–69, 1997.
连结：
6.Angiolella VD, Donato V, Forrester FM, Jeong YT, Pellacani C , Kudo Y, Saraf A, Florens L, Washburn MP, Pagano M. Cyclin F-Mediated Degradation of Ribonucleotide Reductase M2 Controls Genome Integrity and DNA Repair. Cell 149, 1023–1034, 2012. DOI 10.1016/j.cell.2012.03.043
连结：
7. Asangani IA, Rasheed S, Nikolova DA, , Leupold JH, Colburn NH, Post S, Allgayer H. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 27: 2128–2136, 2008.
连结：
8. Bazan V, Migliavacca M, Zanna I, Tubiolo C, Grassi N, Latteri MA. La Farina M. Albanese I, Dardanoni G, Salerno S, Tomasino RM, Labianca R, Gebbia N, Russo A. Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal can¬cer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol 13: 1438–1446, 2002.
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使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。