Zhou Na, Wu Jinhua, Wang Xiang, Sun Zhao, Han Qin, Zhao Lin
Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People's Republic of China.
Tumour Biol. 2016 Feb;37(2):2145-52. doi: 10.1007/s13277-015-3841-0. Epub 2015 Sep 8.
MicroRNAs are predicted to play fundamental roles in the tumorigenesis of hepatocellular carcinoma (HCC). MiR-375 is frequently downregulated in HCC and acts as a tumor suppressor by targeting multiple oncogenes. The objective of this study was to evaluate miR-375 expression and its relevance to the prognosis of HCC. MiR-375 expression was measured in cancerous tissues using qRT-PCR and dichotomized based on a median cutoff. The association between miR-375 expression and clinicopathological parameters and prognosis was subsequently determined. Expression levels of miR-375 were detected in a cohort of 38 HCC patients who underwent curative surgery. No significant correlations were observed between miR-375 expression and clinicopathological parameters, such as gender, age, performance status, preoperative serum AFP level, histological grade, HBV-DNA copy number, ascites, cirrhosis, tumor size, number of tumor nodules, and macrovascular invasion. However, miR-375 expression differs across CLIP scores significantly (p < 0.05). A trend toward poorer disease-free survival (DFS) was observed in patients with lower miR-375 expression compared to those with higher miR-375 expression (p = 0.307). Multivariate analysis demonstrated that low miR-375 expression was an independent prognostic predictor for progression (p = 0.032, risk ratio 3.273). Subgroup analysis revealed that low expression of miR-375 was significantly associated with adverse DFS in patients with poorly differentiated histology, higher serum AFP level (≥400 ng/ml), and advanced tumor stage (CLIP score 1∼3) (p = 0.017, 0.009, and 0.024, respectively). Our study demonstrates that miR-375 expression is significantly correlated with DFS and may be a potential prognostic biomarker of disease progression in HCC.
微小RNA被预测在肝细胞癌(HCC)的肿瘤发生中起重要作用。MiR-375在HCC中经常下调,并通过靶向多个癌基因发挥肿瘤抑制作用。本研究的目的是评估MiR-375的表达及其与HCC预后的相关性。使用qRT-PCR测量癌组织中MiR-375的表达,并根据中位数临界值进行二分法划分。随后确定MiR-375表达与临床病理参数及预后之间的关联。在一组38例行根治性手术的HCC患者中检测了MiR-375的表达水平。未观察到MiR-375表达与临床病理参数之间存在显著相关性,如性别、年龄、体能状态、术前血清AFP水平、组织学分级、HBV-DNA拷贝数、腹水、肝硬化、肿瘤大小、肿瘤结节数量和大血管侵犯。然而,MiR-375表达在CLIP评分中差异显著(p<0.05)。与MiR-375表达较高的患者相比,MiR-375表达较低的患者无病生存期(DFS)有较差的趋势(p=0.307)。多因素分析表明,低MiR-375表达是进展的独立预后预测因素(p=0.032,风险比3.273)。亚组分析显示,MiR-375低表达与组织学分化差、血清AFP水平较高(≥400 ng/ml)和肿瘤晚期(CLIP评分1∼3)患者的不良DFS显著相关(分别为p=0.017、0.009和