Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis
Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis
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全基因组长非编码 RNA 鉴定出一组用于胃癌诊断的新型血浆生物标志物
DOI：
10.1007/s10120-018-00915-7
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发表时间：
2019-07-01
期刊：
影响因子：
7.4
通讯作者：
Zhang, Zhengdong
中科院分区：
文献类型：
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作者：
Zheng, Rui;Liang, Jiayuan;Zhang, Zhengdong
背景虽然长非编码RNA（lncRNA）被认为是用于癌症检测的有用的基于血浆的生物标志物，但lncRNA在胃癌（GC）中的潜在诊断价值仍不清楚。方法为了筛选有前途的GC lncRNA生物标志物，我们对5个GC病例血浆和匹配的健康对照血浆进行了全基因组lncRNA微阵列分析。候选血浆相关 lncRNA 的表达在 446 名受试者的两阶段验证中得到验证。构建受试者工作特征曲线以评估诊断准确性。我们还确定了血浆lncRNA的来源和稳定性，并研究了候选lncRNA对细胞表型的生物学效应。结果共有3878个lncRNA在GC血浆中差异表达，其中选择上调的前10个lncRNA进行进一步验证。两阶段验证显示，GC血浆中三种lncRNA（FAM49B-AS、GUSBP11和CTDHUT）的血浆水平显着高于健康对照（P<0.05），并且这些lncRNA的组合曲线下面积为0.818（95% CI 0.772–0.864）。此外，这些lncRNA在人血浆中稳定且可检测，并且在细胞外液中也富集。与术前相比，根治性手术后第 10 天，所有三种 lncRNA 的表达水平均显着下降（P< 0.05）。此外，lncRNAFAM49B-AS显着促进GC细胞活力和侵袭。结论血浆lncRNAFAM49B-AS、GUSBP11和CTDHUT具有作为GC诊断的无创生物标志物的强大潜力。
BackgroundAlthough long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear.MethodsTo screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes.ResultsA total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, andCTDHUT) were significantly higher in GC plasma as compared with healthy controls (P< 0.05), and the combined area under curve of these lncRNAs was 0.818 (95% CI 0.772–0.864). Moreover, these lncRNAs were stable and detectable in human plasma, and also enriched in extracellular fluid. The expression levels of all three lncRNAs dropped significantly on day 10 after radical surgery compared with preoperative levels (P< 0.05). Also, lncRNAFAM49B-ASsignificantly promoted GC cell viability and invasion.ConclusionsPlasma lncRNAFAM49B-AS, GUSBP11andCTDHUThave a strong potential to serve as noninvasive biomarkers for GC diagnosis.