A network‐based predictive gene expression signature for recurrence risks in stage II colorectal cancer
A network‐based predictive gene expression signature for recurrence risks in stage II colorectal cancer
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基于网络的 II 期结直肠癌复发风险预测基因表达特征
DOI：
10.1002/cam4.2642
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发表时间：
2019-11
期刊：
影响因子：
4
通讯作者：
Guo‐Wang Yang
中科院分区：
文献类型：
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作者：
Wen‐Jing Yang;Hai‐Bo Wang;Wen‐Da Wang;Peng‐Yu Bai;Hong‐Xia Lu;Chang‐He Sun;Zi‐Shen Liu;Ding‐Kun Guan;Gan‐Lin Zhang;Guo‐Wang Yang
目前定义二期结直肠癌复发风险的标准并不健全，因此，我们的目标是探索新的基因标记来预测复发风险并揭示二期结直肠癌的潜在机制。首先，从癌症基因组图谱(TCGA)数据库中获得124例II期结直肠癌患者的基因表达谱，以筛选差异表达基因(Deg)。与非复发组(n=100)相比，复发组(n=24)共发现202个DEGS，其中128个上调，74个下调。在此基础上，通过随机森林变量搜索法确定了前5个基因(ZNF561、WFS1、SLC2A1、MFI2和PTGR1.)，并选择其中的4个(ZNF561、WFS1、SLC2A1和PTGR1.)建立了四基因回归模型，其曲线下面积(AUC)为0.882，并用另一个基因表达谱数据集(GSE12032)进一步验证了该模型的稳健诊断效果，AUC为0.943.GRM对复发的诊断效果与所有阶段的CRC的无病生存率较低有关。此外，基因本体论功能注释和京都百科全书的基因和基因组途径丰富分析显示，18个丰富的功能和6个丰富的途径。4个基因ABCG2、CACNA1F、CYP19A1和Tf通过蛋白质-蛋白质相互作用网络被鉴定为HUB基因，进一步验证了这些基因与结直肠癌各期的不良病理分期和总生存率相关。综上所述，GRM可以有效地将II期CRC分为复发高风险组和低风险组，从而弥补了国家癌症综合网络指南定义的传统临床病理危险因素的预后价值。Hub基因可能是治疗复发的有用靶点。因此，GRM和HUB基因对指导II期大肠癌患者的个体化、精确化治疗方案具有一定的临床价值。
The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four‐gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease‐free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein‐protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.
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DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
影响因子：
11.2
作者：
F. Meggouh;Patrice Lointier;Simone Saez
通讯作者：
F. Meggouh;Patrice Lointier;Simone Saez
影响因子：
3.4
作者：
Kelley RK;Venook AP
通讯作者：
Venook AP
影响因子：
37.3
作者：
Wang L;Shen X;Wang Z;Xiao X;Wei P;Wang Q;Ren F;Wang Y;Liu Z;Sheng W;Huang W;Zhou X;Du X
通讯作者：
Du X
影响因子：
24.5
作者：
Brookes, M. J.;Hughes, S.;Tselepis, C.
通讯作者：
Tselepis, C.