An integrated approach to biomarker discovery reveals gene signatures highly predictive of cancer progression.
An integrated approach to biomarker discovery reveals gene signatures highly predictive of cancer progression.
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DOI：
10.1038/s41598-020-78126-3
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发表时间：
2020-12-04
影响因子：
4.6
通讯作者：
Varghese RT
中科院分区：
文献类型：
--
作者：
Sheng KL;Kang L;Pridham KJ;Dunkenberger LE;Sheng Z;Varghese RT
目前的癌症生物标志物在其预测能力方面存在变异性，并表现出有限的临床疗效，这可能是由于缺乏生物标志物基因与癌症进展的功能相关性。为了应对这一挑战，开发了一个生物标志物发现管道，以整合来自癌症基因组图谱的基因表达谱和来自癌症依赖图谱的必需生存基因数据集，后者对驱动癌症进展的基因进行了编目。通过将该管道应用于肺腺癌、肺鳞状细胞癌和胶质母细胞瘤，鉴定出与癌症进展高度相关的基因，并将其指定为进展基因标签（PGSs）。受试者工作特征曲线下面积的分析显示，PGSs预测患者生存率比以前确定的癌症生物标志物更准确。此外，PGSs对疾病进展的高风险患者进行了分层，这些患者的预后结果更差，癌症进展的频率增加，对化疗的反应较差。这些PGS的稳健性能在来自Gene Expression Omnibus的四个独立的微阵列数据集中被概括，并且在来自胶质母细胞瘤患者的六个新鲜解剖的肿瘤中被进一步验证。我们的研究结果证明了癌症生物标志物发现的综合方法的力量以及将PGS应用于临床生物标志物检测的可能性。
Current cancer biomarkers present variability in their predictive power and demonstrate limited clinical efficacy, possibly due to the lack of functional relevance of biomarker genes to cancer progression. To address this challenge, a biomarker discovery pipeline was developed to integrate gene expression profiles from The Cancer Genome Atlas and essential survival gene datasets from The Cancer Dependency Map, the latter of which catalogs genes driving cancer progression. By applying this pipeline to lung adenocarcinoma, lung squamous cell carcinoma, and glioblastoma, genes highly associated with cancer progression were identified and designated as progression gene signatures (PGSs). Analysis of area under the receiver operating characteristics curve revealed that PGSs predicted patient survival more accurately than previously identified cancer biomarkers. Moreover, PGSs stratified patients with high risk for progressive disease indicated by worse prognostic outcomes, increased frequency of cancer progression, and poor responses to chemotherapy. The robust performance of these PGSs were recapitulated in four independent microarray datasets from Gene Expression Omnibus and were further verified in six freshly dissected tumors from glioblastoma patients. Our results demonstrate the power of an integrated approach to cancer biomarker discovery and the possibility of implementing PGSs into clinical biomarker tests.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
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作者：
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影响因子：
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作者：
Bild, AH;Yao, G;Nevins, JR
通讯作者：
Nevins, JR