Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study
Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study
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DOI：
10.1016/s1470-2045(18)30080-9
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发表时间：
2018-03-01
期刊：
影响因子：
51.1
通讯作者：
Ma, Jun
中科院分区：
文献类型：
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作者：
Tang, Xin-Ran;Li, Ying-Qin;Ma, Jun
背景基因表达模式可用作各种类型癌症的预后生物标志物。我们的目的是确定局部晚期鼻咽癌患者个体远处转移风险评估的基因表达模式。方法在这项多中心、回顾性队列分析中，我们纳入了来自三家中国医院的 937 例局部晚期鼻咽癌患者：中山大学肿瘤中心（中国广州）、桂林医科大学附属医院（中国桂林）和佛山市第一人民医院（中国佛山）。通过微阵列分析，我们分析了中山大学肿瘤医院根治性治疗后有或没有远处转移的 24 对局部晚期鼻咽癌患者的 mRNA 基因表达。在训练队列（广州训练队列；n=410）中使用数字表达谱检查差异表达基因，以使用惩罚回归模型构建基因分类器。我们在一个内部验证队列（广州内部验证队列，n=204）和两个外部独立队列（桂林队列，n=165；佛山队列，n=158）中验证了该基因分类器的预后准确性。主要终点是无远处转移生存期。次要终点是无病生存率和总生存率。结果我们鉴定了转移性和非转移性局部晚期鼻咽癌组织之间的 137 个差异表达基因。生成由 13 个基因组成的局部晚期鼻咽癌 (DMGN) 远处转移基因特征，以将训练队列中的患者分为高风险组和低风险组。训练队列中具有高风险评分的患者的无远处转移生存期较短（风险比 [HR] 4.93，95% CI 2.99-8.16；p
Background Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.Methods In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.Findings We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4.93, 95% CI 2.99-8.16; p