Protein-coding genes combined with long non-coding RNAs predict prognosis in esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional signature
Protein-coding genes combined with long non-coding RNAs predict prognosis in esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional signature
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蛋白质编码基因与长非编码RNA相结合作为一种新的临床多维特征预测食管鳞状细胞癌患者的预后
DOI：
10.1039/c6mb00585c
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发表时间：
2016-01-01
影响因子：
--
通讯作者：
Xu, Li-Yan
中科院分区：
文献类型：
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作者：
Guo, Jin-Cheng;Li, Chun-Quan;Xu, Li-Yan
食管癌是世界范围内恶性程度最高的消化道肿瘤之一，死亡率高。蛋白质编码基因（PCG）和长链非编码RNA（lncRNA）在恶性肿瘤的发生发展中起着重要作用。然而，PCGs联合lncRNA在食管鳞状细胞癌（ESCC）中的临床意义尚待研究。使用探针重新注释、单变量考克斯回归和随机生存森林算法来鉴定预测总体生存的PCG-lncRNA组合，我们发现了由三个PCG组成的签名（ANGPTL 7、OBP 2A、SLC 27 A5）和两种lncRNA（RP 11 -702B10.1，RP 11 -523H24.3）具有最高准确度的预测，训练组的ROC曲线下面积（AUC）为0.85，试验组为0.63，训练组中位生存期为32.2个月，高于对照组的60个月（P < 0.001）。将该特征应用于试验组显示出相似的预后值（中位生存期：39.3个月vs. > 460个月，P = 0.03）。多因素考克斯回归分析显示，三PCG，两lncRNA是影响食管鳞癌患者预后的独立因素。分层分析提示PCG-lncRNA标记结合TNM分期可更准确地对ESCC患者进行分类。我们的研究表明，三-PCG，两个lncRNA签名对食管鳞癌患者的预后有临床意义。该特征可以作为TNM分期的潜在辅助生物标志物，以更精确地细分ESCC患者。
Esophageal carcinoma is one of the most malignant gastrointestinal cancers worldwide, and has a high mortality rate. Both protein-coding genes (PCGs) and long non-coding RNAs (lncRNAs) have been shown to play an important role in the development of malignant tumors. However, the clinical significance of PCGs combined lncRNAs is yet to be investigated in esophageal squamous cell carcinoma (ESCC). Using probe re-annotation, univariable Cox regression and the random survival forest algorithm to identify PCG-lncRNA combinations predictive of the overall survival, we found a signature comprised of three PCGs (ANGPTL7, OBP2A, SLC27A5) and two lncRNAs (RP11-702B10.1, RP11-523H24.3) to have the highest accurate prediction, with an area under ROC curve (AUC) of 0.85 in the training group and 0.63 in the test group, and it was significantly associated with the survival of ESCC patients in the training group (median survival: 32.2 months > 60 months, P < 0.001). The application of the signature to the test group showed similar prognostic values (median survival: 39.3 months vs. > 460 months, P = 0.03). The chi-square test and multivariable Cox regression analysis showed that the three-PCG, two-lncRNA signature was an independent prognostic factor for patients with ESCC. Stratified analysis suggested that the PCG-lncRNA signature combined with the TNM stage could more accurately categorize ESCC patients. Our study suggests that the three-PCG, two-lncRNA signature has clinical significance for the prognosis of patients with ESCC. This signature can serve as a potential auxiliary biomarker of the TNM stage to subdivide ESCC patients more precisely.