DataSheet2_Identification and Validation of a Potent Multi-lncRNA Molecular Model for Predicting Gastric Cancer Prognosis.PDF

Gastric cancer (GC) remains the third deadliest malignancy in China. Despite the current understanding that the long noncoding RNAs (lncRNAs) play a pivotal function in the growth and progression of cancer, their prognostic value in GC remains unclear. Therefore, we aimed to construct a polymolecular prediction model by employing a competing endogenous RNA (ceRNA) network signature obtained by integrated bioinformatics analysis to evaluate patient prognosis in GC. Overall, 1,464 mRNAs, 14,376 lncRNAs, and 73 microRNAs (miRNAs) were found to be differentially expressed in GC. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed RNAs were mostly enriched in neuroactive ligand–receptor interaction, chemical carcinogenesis, epidermis development, and digestion, which were correlated with GC. A ceRNA network consisting of four lncRNAs, 21 miRNAs, and 12 mRNAs were constructed. We identified four lncRNAs (lnc00473, H19, AC079160.1, and AC093866.1) as prognostic biomarkers, and their levels were quantified by qRT-PCR in cancer and adjacent noncancerous tissue specimens. Univariable and multivariable Cox regression analyses suggested statistically significant differences in age, stage, radiotherapy, and risk score groups, which were independent predictors of prognosis. A risk prediction model was created to test whether lncRNAs could be used as an independent risk predictor of GC or not. These novel lncRNAs’ signature independently predicted overall survival in GC (p < 0.001). Taken together, this study identified a ceRNA and protein–protein interaction networks that significantly affect GC, which could be valuable for GC diagnosis and therapy.

胃癌（GC）仍是我国致死率位列第三的恶性肿瘤。尽管目前学界已明确长链非编码RNA（lncRNAs）在肿瘤生长与进展中发挥关键调控作用，但其在胃癌中的预后评估价值仍未明晰。为此，本研究拟通过整合生物信息学分析得到的内源竞争RNA（ceRNA）网络特征，构建多分子预测模型，以评估胃癌患者的预后情况。研究共筛选得到1464个差异表达信使RNA（mRNAs）、14376个长链非编码RNA（lncRNAs）及73个微小RNA（miRNAs）。基因本体（GO）功能富集分析与京都基因与基因组百科全书（KEGG）通路富集分析结果显示，上述差异表达RNA主要富集于神经活性配体-受体相互作用、化学致癌作用、表皮发育及消化过程等与胃癌密切相关的生物学通路与过程。本研究构建了由4个lncRNAs、21个miRNAs及12个mRNAs组成的ceRNA调控网络。最终鉴定出4个可作为预后生物标志物的lncRNAs（lnc00473、H19、AC079160.1与AC093866.1），并通过实时定量聚合酶链反应（qRT-PCR）对癌组织及癌旁正常组织标本中的上述RNA表达水平进行了定量检测。单因素与多因素Cox回归分析表明，年龄、临床分期、放疗状态及风险评分组间存在统计学显著性差异，上述因素均为胃癌预后的独立预测因子。本研究建立了风险预测模型，以验证lncRNAs能否作为胃癌的独立风险预测指标。该新型lncRNA特征可独立预测胃癌患者的总生存期（p < 0.001）。综上，本研究鉴定出可显著影响胃癌发生发展的ceRNA及蛋白质-蛋白质相互作用网络，其可为胃癌的临床诊断与治疗提供潜在的应用价值。