鉴定与肝细胞癌及其不同病因特异性相关的微小RNA面板。

Identifying microRNA panels specifically associated with hepatocellular carcinoma and its different etiologies.

作者信息

Shen Jing, Siegel Abby B, Remotti Helen, Wang Qiao, Santella Regina M

机构信息

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USA.

Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.

出版信息

Hepatoma Res. 2016 Jun;2:151-162. doi: 10.20517/2394-5079.2015.66. Epub 2016 Jun 1.

Abstract

AIM

Deregulation of microRNAs (miRNAs) expression has been identified in hepatocellular carcinoma (HCC), but few results are consistent. The objective of this study is to investigate "HCC tumor type specific" and "tumor common" miRNA panels.

METHODS

The authors integrate and analyze clinical, etiologic and miRNA profiles data from 9 types of solid tumors in The Cancer Genome Atlas (TCGA) and HCC data from Columbia University Medical Center (CUMC).

RESULTS

Levels of 33 miRNAs were significant different between HCC tumor and paired non-tumor tissues (over 2-fold changes) after Bonferroni correction for multiple comparisons, and most (28 miRNAs) were down-regulated in HCC tumors. Using this panel, the authors well classified HCC tumor tissues with 4 misclassifications among 48 paired tissues. Validating this panel in an additional 302 HCC tumor tissues, the authors almost perfectly distinguished tumor from non-tumor tissues with only two misclassifications (99% of HCC tissues correctly classified). Evaluating miRNA profiles in 32 independent HCC paired tissues from CUMC, the authors observed 40 miRNAs significantly deregulated in HCC with over 2-fold changes; 14 overlapped with those identified in TCGA. Subgroup analyses by HCC etiology found that 4 upregulated and 8 downregulated miRNAs were significantly associated with alcohol-related HCC. There were 7 and 4 miRNAs significantly associated with hepatitis B virus- and hepatitis C virus-related HCC, respectively. Data for the first time revealed that miR-24-1, miR-130a and miR-505 were significantly down-regulated only in HCC tumors; miR-142 and miR-455 were significantly down-regulated in HCC, but up-regulated in 5 other solid tumors; suggesting their HCC "tumor type specific" characteristics. A panel of 8 miRNAs was significant in at least 5 tumor types, including HCC, and was identified as "tumor common" marker.

CONCLUSION

The authors concluded that aberrant miRNA panels have HCC "tumor type specificity" and may be affected by etiologic factors.

摘要

目的

肝细胞癌(HCC)中已发现微小RNA(miRNA)表达失调,但很少有结果一致。本研究的目的是调查“HCC肿瘤类型特异性”和“肿瘤共同性”miRNA组。

方法

作者整合并分析了癌症基因组图谱(TCGA)中9种实体瘤的临床、病因和miRNA谱数据以及哥伦比亚大学医学中心(CUMC)的HCC数据。

结果

在进行多重比较的Bonferroni校正后,33种miRNA在HCC肿瘤组织与配对的非肿瘤组织之间存在显著差异(变化超过2倍),且大多数(28种miRNA)在HCC肿瘤中下调。使用该miRNA组,作者在48对配对组织中对HCC肿瘤组织进行了良好分类,仅有4例错误分类。在另外302例HCC肿瘤组织中验证该miRNA组时,作者几乎完美地区分了肿瘤组织与非肿瘤组织,仅有2例错误分类(99%的HCC组织正确分类)。评估来自CUMC的32对独立HCC配对组织中的miRNA谱,作者观察到40种miRNA在HCC中显著失调,变化超过2倍;其中14种与在TCGA中鉴定的miRNA重叠。按HCC病因进行亚组分析发现,4种上调和8种下调的miRNA与酒精相关的HCC显著相关。分别有7种和4种miRNA与乙型肝炎病毒和丙型肝炎病毒相关的HCC显著相关。数据首次显示,miR-24-1、miR-130a和miR-505仅在HCC肿瘤中显著下调;miR-142和miR-455在HCC中显著下调,但在其他5种实体瘤中上调;表明它们具有HCC“肿瘤类型特异性”特征。一组8种miRNA在至少5种肿瘤类型(包括HCC)中显著,被鉴定为“肿瘤共同性”标志物。

结论

作者得出结论,异常的miRNA组具有HCC“肿瘤类型特异性”,可能受病因因素影响。

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