Abstract PR09: The prognostic landscape of genes and infiltrating immune cells across human cancers
Abstract PR09: The prognostic landscape of genes and infiltrating immune cells across human cancers
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DOI：
10.1158/1538-7445.transcagen-pr09
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发表时间：
2015-11
期刊：
影响因子：
11.2
通讯作者：
A. Gentles;Aaron M. Newman;C. Liu;S. Bratman;Weiguo Feng;Dongkyoon Kim;V. Nair;Yue Xu;Amanda Khuong
中科院分区：
文献类型：
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作者：
A. Gentles;Aaron M. Newman;C. Liu;S. Bratman;Weiguo Feng;Dongkyoon Kim;V. Nair;Yue Xu;Amanda Khuong
肿瘤和肿瘤相关细胞的分子谱作为临床结果的生物标志物具有很大的前景。然而，现有的数据集是碎片化的，难以系统地分析。我们提出了一项泛癌症资源和对39种恶性肿瘤中约18,000种人类肿瘤的总体生存结果的表达特征的综合meta分析。虽然三分之一的预后基因是癌症特异性的，但FOXM1调控网络是不良结果的主要预测因子，而有利的预后基因主要反映肿瘤相关的白细胞。使用一种新的计算方法，我们列举了大量肿瘤转录组中的白细胞亚群，揭示了22种不同白细胞与癌症生存之间复杂的新型恶性特异性关联。肿瘤相关的中性粒细胞样多形核细胞和浆细胞是多种实体肿瘤（包括乳腺癌和肺腺癌）的显著但相反的生存预测因子。我们的研究结果引入了新的分析工具，用于描述癌症内部和癌症之间的预后基因和白细胞，并揭示了肿瘤异质性对癌症结果的影响，并应用于发现新的生物标志物和治疗靶点。Andrew J. Gentles, Aaron M. Newman，刘志龙，Scott V. Bratman，冯卫国，金东均，Viswam S. Nair，徐月，Amanda Khuong, Chuong D. Hoang, Maximilian Diehn, Robert B. West, Sylvia K. Plevritis, Ash A. Alizadeh。基因和浸润性免疫细胞在人类癌症中的预后图景。[摘要]。摘自：AACR癌症基因组翻译特别会议论文集；2015年2月7-9日；费城（PA）： AACR；癌症研究2015；75(22增刊1)：摘要nr PR09。
Molecular profiles of tumors and tumor-associated cells hold great promise as biomarkers of clinical outcomes. However, existing datasets are fragmented and difficult to analyze systematically. We present a pan-cancer resource and comprehensive meta-analysis of expression signatures from ~18,000 human tumors with overall survival outcomes across 39 malignancies. While a third of prognostic genes were cancer-specific, a FOXM1 regulatory network is a major predictor of adverse outcomes, while favorably prognostic genes largely reflect tumor-associated leukocytes. Using a novel computational approach, we enumerated leukocyte subsets in bulk tumor transcriptomes, revealing complex novel malignancy-specific associations between 22 distinct leukocytes and cancer survival. Tumor-associated neutrophil-like polymorphonuclear cell and plasmacytic cells emerged as significant but opposite predictors of survival for diverse solid tumors, including breast and lung adenocarcinomas. Our results introduce new analytical tools for delineating prognostic genes and leukocytes within and across cancers, and shed light on the impact of tumour heterogeneity on cancer outcomes, with applications for discovering novel biomarkers and therapeutic targets Citation Format: Andrew J. Gentles, Aaron M. Newman, Chih Long Liu, Scott V. Bratman, Weiguo Feng, Dongkyoon Kim, Viswam S. Nair, Xu Yue, Amanda Khuong, Chuong D. Hoang, Maximilian Diehn, Robert B. West, Sylvia K. Plevritis, Ash A. Alizadeh. The prognostic landscape of genes and infiltrating immune cells across human cancers. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR09.