Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma
Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma
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基于总体生存相关基因表达的风险特征概况及其对透明细胞肾细胞癌的预后影响
DOI：
10.1042/bsr20200492
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发表时间：
2020-08
影响因子：
4
通讯作者：
Guohua Zeng
中科院分区：
文献类型：
--
作者：
Zihao He;Tuo Deng;Xiaolu Duan;Guohua Zeng
摘要 目前的工作旨在评估透明细胞肾细胞癌（ccRCC）中总生存（OS）相关基因的预后价值，并开发供临床使用的列线图。收集来自癌症基因组图谱 (TCGA) 的转录组数据，以筛选 OS > 5 年的 ccRCC 患者（149 名患者）和 OS < 1 年的患者（52 名患者）之间的差异表达基因 (DEG)。在 TCGA 训练集（265 名患者）中，7 个 DEG（细胞色素 P450 家族 3 亚家族 A 成员 7 (CYP3A7)、接触素相关蛋白家族成员 5 (CNTNAP5)、腺苷酸环化酶 2 (ADCY2)、TOX 高迁移率族盒家族成员 3 (TOX3)、纤溶酶原 (PLG)、牙釉质 (ENAM) 和 VII 型胶原 α 1 链(COL7A1)) 被进一步选择，通过最小绝对收缩和选择算子 (LASSO) Cox 回归模型构建预后风险特征。生存分析证实，高风险组的 OS 明显短于低风险组。接下来，单变量和多变量 Cox 回归显示，七个基于基因的风险评分、年龄以及肿瘤、淋巴结和转移分期系统 (TNM) 分期是 OS 的独立预后因素，在此基础上构建了新的列线图，并在 TCGA 验证集（265 名患者）和国际癌症基因组联盟队列（ICGC，84 名患者）中进行验证。列线图具有良好的预测性能，TCGA 训练集、验证集和 ICGC 队列的 C 指数和相应的 95% 置信区间分别为 0.78 (0.74–0.82)、0.75 (0.70–0.80) 和 0.70 (0.60–0.80)。此外，3 年和 5 年生存概率的校准图表明上述三组的曲线拟合性能良好。总之，所提出的基于七个基因特征的列线图是预测 ccRCC OS 的有前途且强大的工具，这可能有助于定制个体化治疗策略。
Abstract The present work aimed to evaluate the prognostic value of overall survival (OS)-related genes in clear cell renal cell carcinoma (ccRCC) and to develop a nomogram for clinical use. Transcriptome data from The Cancer Genome Atlas (TCGA) were collected to screen differentially expressed genes (DEGs) between ccRCC patients with OS > 5 years (149 patients) and those with <1 year (52 patients). In TCGA training set (265 patients), seven DEGs (cytochrome P450 family 3 subfamily A member 7 (CYP3A7), contactin-associated protein family member 5 (CNTNAP5), adenylate cyclase 2 (ADCY2), TOX high mobility group box family member 3 (TOX3), plasminogen (PLG), enamelin (ENAM), and collagen type VII α 1 chain (COL7A1)) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Survival analysis confirmed that the OS in the high-risk group was dramatically shorter than their low-risk counterparts. Next, univariate and multivariate Cox regression revealed the seven genes-based risk score, age, and Tumor, lymph Node, and Metastasis staging system (TNM) stage were independent prognostic factors to OS, based on which a novel nomogram was constructed and validated in both TCGA validation set (265 patients) and the International Cancer Genome Consortium cohort (ICGC, 84 patients). A decent predictive performance of the nomogram was observed, the C-indices and corresponding 95% confidence intervals of TCGA training set, validation set, and ICGC cohort were 0.78 (0.74–0.82), 0.75 (0.70–0.80), and 0.70 (0.60–0.80), respectively. Moreover, the calibration plots of 3- and 5 years survival probability indicated favorable curve-fitting performance in the above three groups. In conclusion, the proposed seven genes signature-based nomogram is a promising and robust tool for predicting the OS of ccRCC, which may help tailor individualized therapeutic strategies.
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个体化免疫相关基因特征可预测透明细胞肾细胞癌患者的免疫状态和肿瘤学结果
DOI：
10.1016/j.urolonc.2019.09.014
发表时间：
2020
影响因子：
2.7
作者：
Ying Xiong;Li Liu;Qi Bai;Yu Xia;Yang Qu;Jiajun Wang;Jianming Guo
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通讯作者：
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