Chang Chiu-Chun, Lin Chun-Che, Wang Chia-Hung, Huang Chi-Chou, Ke Tao-Wei, Wei Po-Li, Yeh Ken-Tu, Hsu Kai-Cheng, Hsu Nan-Yung, Cheng Ya-Wen
Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.
Department of Internal Medicine, Division of Gastroenterology, Chung Shan Medical University Hospital, Taichung 402, Taiwan, R.O.C.
Oncol Lett. 2018 May;15(5):8107-8117. doi: 10.3892/ol.2018.8295. Epub 2018 Mar 19.
Colorectal cancer (CRC) ranks as the third-leading cause of cancer-associated mortalities in Taiwan. The expression of ribonucleotide reductase M2 () and is associated with tumoral malignancy and progression in several types of cancer. The aim of the present study was to determine the association of with the upstream expression of microRNA ( and the association of expression levels of and with clinical outcomes in patients with CRC. The study consisted of 192 tumor tissue samples obtained from patients with CRC. Immunohistochemistry and direct sequencing of DNA were performed to analyze protein expression and / gene mutations in these samples. The expression level of was detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the expression of was lower and that of was higher in patients with lymph node metastasis, distant metastasis, and late-stage CRC compared with patients without lymph node metastasis, distant metastasis and early-stage CRC. A high expression of in patients had a negative effect on overall survival (OS) and disease-free survival (DFS) in CRC. Positive expression of was detected in tumor tissues, and expression associated with the presence of gene mutation. Furthermore, it was detected that the upstream expression was negatively associated with expression in tumor tissues of patients with CRC. expression was associated with survival and tumoral recurrence in patients with mutations. The present authors suggest that the downregulation of and overexpression of in tumor tissues of patients with CRC could be used to predict metastases and disease prognosis, particularly in patients with gene mutations.
结直肠癌(CRC)是台湾地区癌症相关死亡的第三大原因。核糖核苷酸还原酶M2(RRM2)的表达与多种癌症的肿瘤恶性程度和进展相关。本研究的目的是确定RRM2与微小RNA(miR-122和miR-145)上游表达的关联,以及RRM2和miR-145的表达水平与CRC患者临床结局的关联。该研究包括从CRC患者获取的192份肿瘤组织样本。对这些样本进行免疫组织化学和DNA直接测序,以分析RRM2蛋白表达和RRM2/miR-145基因突变。通过逆转录定量聚合酶链反应检测miR-122的表达水平。结果显示,与无淋巴结转移、远处转移和早期CRC的患者相比,有淋巴结转移、远处转移和晚期CRC的患者中RRM2的表达较低,而miR-145的表达较高。患者中RRM2的高表达对CRC的总生存期(OS)和无病生存期(DFS)有负面影响。在肿瘤组织中检测到RRM2的阳性表达,且表达与RRM2基因突变的存在相关。此外,检测到CRC患者肿瘤组织中miR-122的上游表达与RRM2表达呈负相关。RRM2表达与RRM2基因突变患者的生存和肿瘤复发相关。本研究作者认为,CRC患者肿瘤组织中RRM2的下调和miR-145的过表达可用于预测转移和疾病预后,特别是在RRM2基因突变的患者中。