Molecular-Subtype-Specific Biomarkers Improve Prediction of Prognosis in Colorectal Cancer
Molecular-Subtype-Specific Biomarkers Improve Prediction of Prognosis in Colorectal Cancer
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DOI：
10.1016/j.celrep.2017.04.045
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发表时间：
2017-05-09
期刊：
影响因子：
8.8
通讯作者：
Andersen, Claus Lindbjerg
中科院分区：
文献类型：
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作者：
Bramsen, Jesper Bertram;Rasmussen, Mads Heilskov;Andersen, Claus Lindbjerg
结直肠癌（CRC）的特点是肿瘤间的主要多样性，使疾病和治疗结果的预测复杂化。最近的努力有助于解决这一问题的亚分类CRC到自然分子亚型，但是，这种策略还不能为临床医生提供更好的决策工具。我们在这里提出了一个扩展的框架CRC分层，专门旨在提高患者的诊断。使用来自1，100个CRC的转录谱，包括> 300个先前未发表的样本，我们确定了癌细胞和肿瘤原型，并表明肿瘤微环境是可能受微生物组影响的主要预后决定因素。值得注意的是，我们的分型策略允许鉴定原型特异性预后生物标志物，其提供的信息超出并独立于UICC-TNM分期、MSI状态和共有分子分型。结果表明，我们的扩展亚型框架，结合亚型和亚型特异性生物标志物，可能有助于改善患者的诊断，并可能为未来的研究奠定坚实的基础。
Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC into natural molecular subtypes; however, this strategy is not yet able to provide clinicians with improved tools for decision making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including > 300 previously unpublished samples, we identify cancer cell and tumor archetypes and suggest the tumor micro-environment as a major prognostic determinant that can be influenced by the microbiome. Notably, our subtyping strategy allowed identification of arche-type-specific prognostic biomarkers that provided information beyond and independent of UICC-TNM staging, MSI status, and consensus molecular subtyping. The results illustrate that our extended subtyping framework, combining subtyping and subtype-specific biomarkers, could contribute to improved patient prognostication and may form a strong basis for future studies.