人类胃癌中长链非编码 RNA 的表达谱及其临床意义。
Long non-coding RNA expression profile in human gastric cancer and its clinical significances.
机构信息
Department of Biochemistry and Molecular Biology, and Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
出版信息
J Transl Med. 2013 Sep 24;11:225. doi: 10.1186/1479-5876-11-225.
BACKGROUND
Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value.
METHODS
The global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases.
RESULTS
Total of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively.
CONCLUSIONS
The lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.
背景
长链非编码 RNA（lncRNA）广泛转录于基因组中，但它们在人类癌症中的潜在作用尚不清楚。本研究旨在确定胃癌中的 lncRNA 表达谱及其潜在的临床价值。
方法
通过 lncRNA 微阵列测量胃癌中的全局 lncRNA 表达谱。通过实时逆转录-聚合酶链反应（RT-PCR）验证两种代表性 lncRNA（H19 和 uc001lsz）的水平。探讨它们的水平与胃癌患者临床病理因素之间的关系。构建了用于区分胃癌与良性胃部疾病的受试者工作特征（ROC）曲线。
结果
发现肿瘤组织与非肿瘤组织之间差异表达水平超过两倍的总共有 135 个 lncRNA（GEO 编号：GSE47850）。胃癌组织中下调最明显的 lncRNA 是 FER1L4、uc001lsz、BG491697、AF131784、uc009ycs、BG981369、AF147447、HMlincRNA1600 和 AK054588；而上调最明显的是 H19、HMlincRNA717、BM709340、BQ213083、AK054978 和 DB077273。H19 在胃和肝癌细胞系中高表达，而在肺癌和前列腺癌细胞系中低表达。uc001lsz 在胃癌、肺癌和肝癌细胞系中低表达，而在前列腺癌细胞系中高表达。H19、uc001lsz 和组合的 ROC 曲线下面积分别高达 0.613、0.751 和 0.761。
结论
胃癌中的 lncRNA 表达谱提示 lncRNA 在胃癌发生发展中的潜在作用。H19 在胃癌中的高表达提示 H19 可能参与胃癌的发生。uc001lsz 在胃癌细胞系和组织中的低表达及其与 TNM 分期的关系，以及在早期癌症和癌前病变中的失调，提示 uc001lsz 可能是早期胃癌诊断的潜在标志物。
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