Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Gastrointestinal Surgery, Shaoxing People's Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing, Zhejiang, China.
EBioMedicine. 2020 Nov;61:103023. doi: 10.1016/j.ebiom.2020.103023. Epub 2020 Oct 14.
We previously established a 53-gene prognostic signature for overall survival (OS) of gastric cancer patients. This retrospective multi-center study aimed to develop a clinically applicable gene expression detection assay and to investigate the prognostic value of this signature.
A TCGA gastric adenocarcinoma cohort (TCGA-STAD) was used for comparing 53-gene signature with other gene signatures. A high-throughput mRNA hybridization gene expression assay was developed to quantify the expression of 53-genes in formalin-fixed paraffin-embedded tissues of 540 patients enrolled from three hospitals. 180 patents were randomly selected from two hospitals to build a prognostic prediction model based on the 53-gene signature using leave-p-out (one-third out) cross-validation method together with Cox regression and Kaplan-Meier analysis, and the model was assessed on three validation cohorts.
In the evaluation phase, studies based on TCGA-STAD showed that the 53-gene signature was significantly superior to other three prognostic signatures and was independent of TCGA molecular subtypes and clinical factors. For clinical validation and utility, the prognostic scores were generated using the newly developed assay, which was reliable and sensitive, in 100 sampling training sets and were significantly associated with OS in 100 sampling validation sets. The scores were significantly associated with OS in three independent and combined validation cohorts, and in patients with stages II and III/IV. The multivariate Cox regression demonstrated that the prognostic power of the score was independent of clinical factors, consistent with those findings in the TCGA dataset. Finally, patients with good prognostic scores exhibited significantly a better 5-year OS rate from adjuvant FOLFOX chemotherapy after surgery than from other chemotherapies.
The 53-gene prognostic score system is clinically applicable for predicting the OS of patients independent of clinical factors in gastric cancers, which could also be a promising predictive biomarker for FOLFOX regimen.
Chinese National Science and Technology, National Natural Science Foundation and Natural Science Foundation of Jiangsu Province.
我们之前建立了一个用于预测胃癌患者总生存期（OS）的 53 基因预后标志物。本回顾性多中心研究旨在开发一种临床适用的基因表达检测方法，并研究该标志物的预后价值。
使用 TCGA 胃腺癌队列（TCGA-STAD）比较 53 基因标志物与其他基因标志物。开发了一种高通量 mRNA 杂交基因表达检测方法，用于定量检测 540 例来自三所医院的患者福尔马林固定石蜡包埋组织中 53 个基因的表达。从两所医院中随机选择 180 例患者，使用三分之一样本外（leave-p-out）交叉验证方法，结合 Cox 回归和 Kaplan-Meier 分析，基于 53 基因标志物构建预后预测模型，并在三个验证队列中进行评估。
在评估阶段，基于 TCGA-STAD 的研究表明，53 基因标志物明显优于其他三种预后标志物，且与 TCGA 分子亚型和临床因素无关。为了进行临床验证和实用性研究，我们使用新开发的检测方法生成了预后评分，该方法在 100 个采样训练集中具有可靠性和敏感性，且在 100 个采样验证集中与 OS 显著相关。评分在三个独立的和合并的验证队列中与 OS 显著相关，且在 II 期和 III/IV 期患者中也与 OS 显著相关。多变量 Cox 回归表明，评分的预后能力与临床因素独立，与 TCGA 数据集的结果一致。最后，手术后接受辅助 FOLFOX 化疗的预后评分良好的患者，其 5 年 OS 率明显高于其他化疗方案。
53 基因预后评分系统在预测胃癌患者的 OS 方面具有临床适用性，与临床因素无关，也可能是 FOLFOX 方案的有前途的预测生物标志物。
中国国家科学技术、国家自然科学基金和江苏省自然科学基金。
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