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提高整体生存预后预测准确性:CRC 患者的 9 基因标志物。

Improving the overall survival prognosis prediction accuracy: A 9-gene signature in CRC patients.

机构信息

Department of General Surgery & Guangdong Province Key Laboratory of Precision Medicine for Gastrointestinal Tumor, The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Obstetrics and Gynaecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Cancer Med. 2021 Sep;10(17):5998-6009. doi: 10.1002/cam4.4104. Epub 2021 Aug 4.

Abstract

Colorectal cancer (CRC) is a malignant tumor and morbidity rates are among the highest in the world. The variation in CRC patients' prognosis prompts an urgent need for new molecular biomarkers to improve the accuracy for predicting the CRC patients' prognosis or as a complement to the traditional TNM staging for clinical practice. CRC patients' gene expression data of HTSeq-FPKM and matching clinical information were downloaded from The Cancer Genome Atlas (TCGA) datasets. Patients were randomly divided into a training dataset and a test dataset. By univariate and multivariate Cox regression survival analyses and Lasso regression analysis, a prediction model which divided each patient into high-or low-risk group was constructed. The differences in survival time between the two groups were compared by the Kaplan-Meier method and the log-rank test. The weighted gene co-expression network analysis (WGCNA) was used to explore the relationship between all the survival-related genes. The survival outcomes of patients whose overall survival (OS) time were significantly lower in the high-risk group than that in the low-risk group both in the training and test datasets. Areas under the ROC curves which termed AUC values of our 9-gene signature achieved 0.823 in the training dataset and 0.806 in the test dataset. A nomogram was constructed for clinical practice when we combined the 9-gene signature with TNM stage and age to evaluate the survival time of patients with CRC, and the C-index increased from 0.739 to 0.794. In conclusion, we identified nine novel biomarkers that not only are independent prognostic indexes for CRC patients but also can serve as a good supplement to traditional clinicopathological factors to more accurately evaluate the survival of CRC patients.

摘要

结直肠癌(CRC)是一种恶性肿瘤,发病率在世界范围内位居前列。CRC 患者预后的差异促使我们迫切需要新的分子生物标志物,以提高预测 CRC 患者预后的准确性,或作为传统 TNM 分期的补充,应用于临床实践。我们从癌症基因组图谱(TCGA)数据集下载了结直肠癌患者的 HTSeq-FPKM 基因表达数据和匹配的临床信息,并将患者随机分为训练数据集和测试数据集。通过单变量和多变量 Cox 回归生存分析和 Lasso 回归分析,构建了一个将每个患者分为高风险或低风险组的预测模型。通过 Kaplan-Meier 方法和对数秩检验比较两组之间的生存时间差异。采用加权基因共表达网络分析(WGCNA)探讨所有与生存相关基因之间的关系。在训练和测试数据集,整体生存(OS)时间明显较低的高风险组患者的生存结局都显著低于低风险组。我们 9 基因特征的 ROC 曲线下面积(AUC)在训练数据集和测试数据集分别达到 0.823 和 0.806。当我们将 9 基因特征与 TNM 分期和年龄相结合,构建用于评估 CRC 患者生存时间的列线图时,C 指数从 0.739 增加到 0.794。总之,我们确定了 9 个新的生物标志物,它们不仅是 CRC 患者独立的预后指标,而且可以作为传统临床病理因素的良好补充,以更准确地评估 CRC 患者的生存情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f344/8419765/bbbc21da81b7/CAM4-10-5998-g010.jpg

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