miR-17的过表达与结直肠癌肝转移相关。
Overexpression of miR-17 is correlated with liver metastasis in colorectal cancer.
作者信息
Lai Hao, Zhang Jie, Zuo Hongqun, Liu Haizhou, Xu Jing, Feng Yan, Lin Yuan, Mo Xianwei
机构信息
Gastrointestinal Surgery Department, Guangxi Medical University Cancer Hospital.
Guangxi Clinical Research Center for Colorectal Cancer.
出版信息
Medicine (Baltimore). 2020 Feb;99(9):e19265. doi: 10.1097/MD.0000000000019265.
BACKGROUND
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in men and women. The presence of systemic disease, with metastatic spread to distant sites such as the liver, considerably reduces the survival rate in CRC. Cancer stem cells contribute to the metastatic potential of CRC. However, the mechanism underlying metastasis in CRC remains unclear. Thus, this study aimed to examine the expression of microRNAs (miRNAs) in CRC stem cells in cases of liver metastases and assess their correlation with clinicopathological features.
METHODS
miRNAs showing high expression in liver metastases and primary lesions were selected through data mining of gene expression omnibus datasets, and miRNAs characteristic of stem cells were selected through COREMINE medical text mining. Subsequently, paired formalin-fixed paraffin-embedded tissue samples of primary CRC and liver metastasis from 30 patients were examined for the expression of miRNAs common to these lists (hsa-miR-20a, hsa-miR-26b, hsa-miR-146a, hsa-miR-17, hsa-miR-451, hsa-miR-23a, and hsa-miR-29a) using quantitative real-time polymerase chain reaction. Further, miRNA expression was compared between liver metastases and the primary tumor in each patient and the factors associated with differential expression were analyzed.
RESULTS
hsa-miR-17 was significantly upregulated in liver metastases (P < .05), but no significant difference in the expression of hsa-miR-26b, hsa-miR-146a, hsa-miR-451, hsa-miR-23a, and hsa-miR-29a was observed between primary tumors and liver metastases. The higher expression of hsa-miR-17 in liver metastases was associated with the administration of neoadjuvant chemotherapy and tumor differentiation (P < .05) but was not associated with age, sex, tumor location, or lymphatic metastasis.
CONCLUSIONS
High expression of miR-17 may contribute to liver metastasis in CRC. Therefore, an in-depth understanding of its downstream pathways could help in elucidating the mechanisms underlying liver metastases in CRC. However, additional studies are warranted to validate these findings.
背景
结直肠癌（CRC）是男性和女性癌症相关死亡的第二大主要原因。存在全身疾病，伴有转移至肝脏等远处部位，会显著降低CRC患者的生存率。癌症干细胞促成了CRC的转移潜能。然而，CRC转移的潜在机制仍不清楚。因此，本研究旨在检测肝转移病例中CRC干细胞中微小RNA（miRNA）的表达，并评估其与临床病理特征的相关性。
方法
通过对基因表达综合数据集进行数据挖掘，筛选出在肝转移灶和原发灶中高表达的miRNA，并通过COREMINE医学文本挖掘筛选出干细胞特征性miRNA。随后，使用定量实时聚合酶链反应检测30例患者的原发性CRC和肝转移灶的配对福尔马林固定石蜡包埋组织样本中这些列表中共有的miRNA（hsa-miR-20a、hsa-miR-26b、hsa-miR-146a、hsa-miR-17、hsa-miR-451、hsa-miR-23a和hsa-miR-29a）的表达。此外，比较了每位患者肝转移灶与原发肿瘤之间的miRNA表达，并分析了与差异表达相关的因素。
结果
hsa-miR-17在肝转移灶中显著上调（P<0.05），但在原发肿瘤和肝转移灶之间，hsa-miR-26b、hsa-miR-146a、hsa-miR-451、hsa-miR-23a和hsa-miR-29a的表达未观察到显著差异。肝转移灶中hsa-miR-17的高表达与新辅助化疗的应用和肿瘤分化相关（P<0.05），但与年龄、性别、肿瘤位置或淋巴转移无关。
结论
miR-17的高表达可能促成CRC的肝转移。因此，深入了解其下游途径有助于阐明CRC肝转移的潜在机制。然而，需要更多研究来验证这些发现。
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