A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients
A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients
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DOI：
10.1016/j.molonc.2014.06.016
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发表时间：
2014-12-01
影响因子：
6.6
通讯作者：
Kim, Jin Cheon
中科院分区：
文献类型：
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作者：
Kim, Seon-Kyu;Kim, Seon-Young;Kim, Jin Cheon
结直肠癌（CRC）患者经常经历疾病复发和远处转移。本研究的目的是确定预后指标，包括个体对化疗的反应，在结直肠癌患者。使用来自18名CRC患者的54个样品（正常结肠、原发性CRC和肝转移）生成RNA-seq数据，并鉴定了与CRC侵袭性相关的基因。在四个独立的CRC患者队列（n = 1063）中开发并验证了基于这些基因的风险评分。应用多种统计方法验证风险评分系统，包括广义线性模型似然比检验、Kaplan-Meier曲线、对数秩检验和考克斯模型。TREM 1和CTGF被鉴定为与CRC侵袭性相关的两种激活的调节因子。基于由TREM 1或CTGF激活（TCA 19）调节的19个基因的风险评分是重要的预后指标。在基于病理分期的多变量和子集分析中，TCA 19是一个独立的危险因素（HR = 1.894，95%CI = 1.227-2.809，P = 0.002）。III期患者的亚组分层显示，TCA 19具有预后潜力，并确定了无论年龄如何都能从辅助化疗中获益的患者。TCA 19预测因子代表了一种新的诊断工具，用于识别高危CRC患者并可能预测对辅助化疗的反应。(C)2014年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Colorectal cancer (CRC) patients frequently experience disease recurrence and distant metastasis. This study aimed to identify prognostic indicators, including individual responses to chemotherapy, in CRC patients. RNA-seq data was generated using 54 samples (normal colon, primary CRC, and liver metastases) from 18 CRC patients and genes associated with CRC aggressiveness were identified. A risk score based on these genes was developed and validated in four independent CRC patient cohorts (n = 1063). Diverse statistical methods were applied to validate the risk scoring system, including a generalized linear model likelihood ratio test, Kaplan-Meier curves, a log-rank test, and the Cox model. TREM1 and CTGF were identified as two activated regulators associated with CRC aggressiveness. A risk score based on 19 genes regulated by TREM1 or CTGF activation (TCA19) was a significant prognostic indicator. In multivariate and subset analyses based on pathological staging, TCA19 was an independent risk factor (HR = 1.894, 95% CI = 1.227-2.809, P = 0.002). Subset stratification in stage III patients revealed that TCA19 had prognostic potential and identified patients who would benefit from adjuvant chemotherapy, regardless of age. The TCA19 predictor represents a novel diagnostic tool for identifying high-risk CRC patients and possibly predicting the response to adjuvant chemotherapy. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.