Chen Shangxiang, Lao Jiawen, Geng Qirong, Zhang Ji, Wu Aiwen, Xu Dazhi
Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Front Oncol. 2020 Jun 19;10:565. doi: 10.3389/fonc.2020.00565. eCollection 2020.
Current staging systems are inadequate for evaluating the prognosis of patients with locally advanced gastric cancer (LAGC, stages II-III). Therefore, we developed a serum microRNA (miRNA) signature to facilitate individualized management of these patients. Using microarray analysis, we analyzed 12 serum specimens based on different prognoses (good survival group, = 7; poor survival group, = 5). We identified and confirmed differential expression of these miRNAs using quantitative reverse transcription PCR (qRT-PCR) of serum from 51 patients with LAGC. A three miRNA-based classifier was established as a training set by Cox proportional hazard regression and risk-score analysis. We validated the prognostic accuracy of this model in an internal validation cohort (Sun Yat-Sen University Cancer Center, SYSUCC validation cohort, = 50) and an external independent cohort (Beijing Cancer Hospital, BJCH cohort, = 67). Three miRNAs were found to be associated with survival of LAGC ( < 0.001 for miR-132, = 0.011 for miR-548a-3p, and < 0.001 for miR-1826). A three-miRNA signature was developed for the training set, and a significant difference was found between the survival of low- and high-risk score patients ( < 0.01). The combination of the miRNA signature and tumor-node-metastasis (TNM) stage exhibited superior discrimination. Consistent results were obtained by further validation of the internal set and the BJCH set, which confirmed the predictive value of the model. We built an easy-to-use prognostic signature using three serum miRNAs as markers. Our miRNA signature may improve postoperative risk stratification and serve as a complement to the TNM staging system.
目前的分期系统不足以评估局部晚期胃癌(LAGC,II - III期)患者的预后。因此,我们开发了一种血清微小RNA(miRNA)特征,以促进对这些患者的个体化管理。通过微阵列分析,我们基于不同预后分析了12份血清标本(生存良好组,n = 7;生存较差组,n = 5)。我们使用51例LAGC患者血清的定量逆转录PCR(qRT-PCR)鉴定并确认了这些miRNA的差异表达。通过Cox比例风险回归和风险评分分析,建立了一个基于三个miRNA的分类器作为训练集。我们在内部验证队列(中山大学肿瘤防治中心,SYSUCC验证队列,n = 50)和外部独立队列(北京肿瘤医院,BJCH队列,n = 67)中验证了该模型的预后准确性。发现三个miRNA与LAGC患者的生存相关(miR-132,P < 0.001;miR-548a-3p,P = 0.011;miR-1826,P < 0.001)。为训练集开发了一个三miRNA特征,低风险和高风险评分患者的生存之间存在显著差异(P < 0.01)。miRNA特征与肿瘤-淋巴结-转移(TNM)分期的组合表现出更好的区分度。通过对内部数据集和BJCH数据集的进一步验证获得了一致的结果,证实了该模型的预测价值。我们使用三种血清miRNA作为标志物构建了一个易于使用的预后特征。我们的miRNA特征可能会改善术后风险分层,并作为TNM分期系统的补充。