Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Department of Gastroenterology, Jing'an District Center Hospital of Shanghai (Huashan Hospital, Fudan University, Jing'an Branch), Shanghai 200040, P.R. China.
Oncol Rep. 2018 Mar;39(3):1338-1346. doi: 10.3892/or.2017.6163. Epub 2017 Dec 19.
Early detection of gastric cancer (GC) is crucial to improve the therapeutic effect and prolong the survival of patients. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs that function as repressors of diverse genes. We aimed to identify a microRNA panel in the serum of patients to predict GC non-invasively with high accuracy and sensitivity. Using six types of classifiers, we selected three markers (miR‑21-5p, miR-22-3p and miR-29c-3p) from a published miRNA profiling study (GSE23739) which was treated as a training set. The values of the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.9437, 0.9456 and 0.9563 in the three classifiers [Compound covariate classifier, Diagonal linear discriminant analysis (DLDA) classifier and Support vector machine classifier], respectively. Then the panel was validated further in another two miRNA profiles in GEO (Gene Expression Omnibus) databases (GSE26595, GSE28700) with high AUC values as well. Next, we found that the serum levels of miR-21 were significantly higher in GC patients than levels in healthy controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for confirmation, which was opposite to the serum levels of miR-22 and miR-29c (all P<0.0001). Finally, using bioinformatic tools, their biological mechanisms were elucidated by their predicted targets: Sp1 (miR-21) and PTEN (miR-22 and miR-29c). This miRNA panel is a non‑invasive and potential biomarker for GC.
早期发现胃癌（GC）对于提高治疗效果和延长患者生存时间至关重要。微小 RNA（miRNA）是一组小的非蛋白编码 RNA，作为多种基因的抑制剂发挥作用。我们旨在通过识别患者血清中的 miRNA 谱，以高准确性和敏感性无创预测 GC。使用六种类型的分类器，我们从发表的 miRNA 分析研究（GSE23739）中选择了三个标志物（miR-21-5p、miR-22-3p 和 miR-29c-3p）作为训练集。在三个分类器[复合协变量分类器、对角线线性判别分析（DLDA）分类器和支持向量机分类器]中，ROC 曲线（AUC）的 AUC 值分别为 0.9437、0.9456 和 0.9563。然后，该面板在 GEO（基因表达综合数据库）数据库中的另外两个 miRNA 图谱（GSE26595、GSE28700）中得到了进一步验证，AUC 值也很高。接下来，我们通过定量逆转录聚合酶链反应（qRT-PCR）发现，GC 患者的血清 miR-21 水平明显高于健康对照组（均 P<0.0001），而血清 miR-22 和 miR-29c 水平则相反。最后，通过生物信息学工具，根据其预测靶点：Sp1（miR-21）和 PTEN（miR-22 和 miR-29c），阐明了它们的生物学机制。该 miRNA 谱是 GC 的一种非侵入性和潜在的生物标志物。
