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与肺癌死亡率相关的生物标志物被发现
作者:小柯机器人 发布时间:2019/10/9 14:30:50

英国伦敦大学学院癌症研究所Charles Swanton、Nicholas McGranahan和Nicolai J. Birkbak等研究人员合作发现,一种克隆型表达的生物标志物与肺癌死亡率相关。2019年10月7日,这一研究成果在线发表在国际学术期刊《自然—医学》上。

研究人员分析了TRACERx研究中48位患者的156个肿瘤区域的多区域全外显子组和RNA测序数据,以探索和控制非小细胞肺癌中转录组肿瘤内异质性(RNA-ITH)的发生。研究人员发现染色体不稳定是RNA-ITH的主要原因,并且现有的预后基因表达特征容易受到肿瘤取样偏倚的影响。为了解决这个问题,研究人员确定了在单个肿瘤中均质表达的基因,这些基因编码癌细胞增殖的表达模块,并且通常受肿瘤发展早期选择的DNA拷贝数增加的驱动。克隆转录组生物标志物克服了肿瘤取样的偏倚,与独立于临床病理风险因素的存活率相关,并可能提供一种完善策略,以跨癌症类型优化生物标志物的设计。

据介绍,分子生物标志物的目的是将癌症患者分为有预测结局的疾病亚型,从而提高诊断准确性,使其超越诸如肿瘤分期等临床指标。RNA-ITH已被证明可以混淆多种癌症类型中现有表达型生物标记物。

附:英文原文

Title: A clonal expression biomarker associates with lung cancer mortality

Author: Dhruva Biswas, Nicolai J. Birkbak, Rachel Rosenthal, Crispin T. Hiley, Emilia L. Lim, Krisztian Papp, Stefan Boeing, Marcin Krzystanek, Dijana Djureinovic, Linnea La Fleur, Maria Greco, Balzs Dme, Jnos Fillinger, Hans Brunnstrm, Yin Wu, David A. Moore, Marcin Skrzypski, Christopher Abbosh, Kevin Litchfield, Maise Al Bakir, Thomas B. K. Watkins, Selvaraju Veeriah, Gareth A. Wilson, Mariam Jamal-Hanjani, Judit Moldvay, Johan Botling, Arul M. Chinnaiyan, Patrick Micke, Allan Hackshaw, Jiri Bartek, Istvan Csabai, Zoltan Szallasi, Javier Herrero, Nicholas McGranahan, Charles Swanton

Issue&Volume: 2019-10-07

Abstract: 

An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage1. Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types2,3,4,5,6. Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.

DOI: 10.1038/s41591-019-0595-z

Source: https://www.nature.com/articles/s41591-019-0595-z

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex