Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Gastric Cancer. 2019 Jul;22(4):731-741. doi: 10.1007/s10120-018-00915-7. Epub 2019 Jan 2.
Although 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.
To 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.
A 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, and CTDHUT) 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, lncRNA FAM49B-AS significantly promoted GC cell viability and invasion.
Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.
尽管长链非编码 RNA（lncRNA）被认为是用于癌症检测的有价值的血浆生物标志物，但 lncRNA 在胃癌（GC）中的潜在诊断价值仍不清楚。
为了筛选用于 GC 的有前途的 lncRNA 生物标志物，我们在 5 例 GC 病例的血浆与匹配的健康对照者血浆之间进行了全基因组 lncRNA 微阵列分析。在 446 例受试者的两阶段验证中验证了候选血浆相关 lncRNA 的表达。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影响。
GC 血浆中共有 3878 个 lncRNA 表达差异，其中选择了前 10 个上调的 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）的血浆水平明显高于健康对照者（P < 0.05），并且这些 lncRNA 的联合曲线下面积为 0.818（95%CI 0.772-0.864）。此外，这些 lncRNA 在人血浆中稳定且可检测，并且在细胞外液中富集。与术前水平相比，根治性手术后第 10 天，所有三种 lncRNA 的表达水平均明显下降（P < 0.05）。此外，lncRNA FAM49B-AS 显著促进 GC 细胞活力和侵袭。
血浆 lncRNA FAM49B-AS、GUSBP11 和 CTDHUT 具有作为 GC 诊断的非侵入性生物标志物的强大潜力。
