Prognostic and predictive value of an autophagy-related signature for early relapse in stages I-III colon cancer
Prognostic and predictive value of an autophagy-related signature for early relapse in stages I-III colon cancer
复制标题
自噬相关特征对 I-III 期结肠癌早期复发的预后和预测价值
DOI：
10.1093/carcin/bgz031
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发表时间：
2019-07-01
期刊：
影响因子：
4.7
通讯作者：
Cai, Guoxiang
中科院分区：
文献类型：
--
作者：
Mo, Shaobo;Dai, Weixing;Cai, Guoxiang
我们假设自噬相关基因的表达差异有助于对手术后早期复发的风险进行分层，并评估I-III期结肠癌患者的预后。因此，对GSE 39582测试系列和内部验证系列中早期复发组和长期生存组的患者进行倾向评分匹配分析。使用考克斯回归模型，建立了九个自噬相关标签（CAPN 2、ATG 16 L2、TP 63、SIRT 1、RPS 6 KB 1、PEX 3、ATG 5、UVRAG、NAF 1），以将患者分为早期复发的高风险（高风险组）和早期复发的低风险（低风险组）。两组的无复发生存率（RFS）经检验[危险比（HR）：2.019，95%可信区间（CI）：1.362-2.992，P < 0.001]，内部验证有显著性差异（HR：2.464，95%CI：1.196-5.079，P < 0.001）和另外两个外部验证系列（GSE 14333-HR：2.250，95% CI：1.227-4.126，P = 0.007; GSE 33113-HR：5.552，95% CI：2.098-14.693，P < 0.001）。然后，基于RFS，我们开发了一个诺模图，整合了九个自噬相关分类器和四个临床病理危险因素，以评估I-III期结肠癌患者的预后。2年时的时间依赖性受试者工作曲线显示，综合特征（曲线下面积= 0.758）比美国癌症联合委员会TNM分期（曲线下面积= 0.620）具有更好的预后准确性。总之，我们确定并建立了一个九自噬相关的签名，这是一种可靠的方法来预测I-III期结肠癌患者的早期复发，可以帮助医生设计更有效的治疗策略。
We postulated that expression differences of autophagy-related genes are instrumental in stratifying the risk of early relapse after surgery and evaluating the prognosis of patients with stages I-III colon cancer. Therefore, propensity score matching analysis was performed between patients in early relapse group and long-term survival group from GSE39582 test series and internal validation series. Using Cox regression model, a nine-autophagy-related signature (CAPN2, ATG16L2, TP63, SIRT1, RPS6KB1, PEX3, ATG5, UVRAG, NAF1) was established to classify patients into those at high risk of early relapse (high-risk group), and those at low risk of early relapse (low-risk group). Relapse-free survival (RFS) was significantly different between the two groups in test [hazard ratio (HR): 2.019, 95% confidence interval (CI): 1.362-2.992, P < 0.001], internal validation (HR: 2.464, 95% CI: 1.196-5.079, P < 0.001) and another two external validation series (GSE14333-HR: 2.250, 95% CI: 1.227-4.126, P = 0.007; GSE33113-HR: 5.552, 95% CI: 2.098-14.693, P < 0.001). Then, based on RFS, we developed a nomogram, integrating the nine-autophagy-related classifier and four clinicopathological risk factors to evaluate prognosis of stages I-III colon cancer patients. Time-dependent receiver operating curve at 2 years showed that the integrated signature (area under curve = 0.758) had better prognostic accuracy than American Joint Committee on Cancer TNM stage (area under curve = 0.620). In conclusion, we identified and built a nine-autophagy-related signature, a credible approach to early relapse prediction in stages I-III colon cancer patients, which can assist physicians in devising more efficient therapeutic strategies.