Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.
Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.
复制标题
DOI：
10.1371/journal.pcbi.1004115
复制
发表时间：
2015-03
影响因子：
4.3
通讯作者：
Teschendorff AE
中科院分区：
文献类型：
--
作者：
Banerji CR;Severini S;Caldas C;Teschendorff AE
癌症干细胞假说，即一小部分肿瘤细胞负责肿瘤的发生和癌症的进展，正在被广泛接受，最近的证据表明这些细胞具有预后和预测作用。肿瘤内异质性，即单个患者肿瘤内癌细胞群的多样性，与癌症干细胞有关，也被认为是肿瘤学的潜在预后指标。然而，以临床相关的方式测量癌症干细胞丰度和肿瘤内异质性，目前提出了一个挑战。在这里，我们提出信号熵，从样本的全基因组基因表达谱衍生的信号通路滥交的测量，作为肿瘤样本的干性的估计。通过考虑超过500种不同细胞表达谱的混合物，我们发现信号熵也与肿瘤内异质性相关。通过分析3668例乳腺癌和1692例肺腺癌样本，我们进一步证明信号熵与生存率呈负相关，优于领先的基于临床基因表达的预后工具。信号熵被发现是一种一般的预后测量，在不同的乳腺癌临床亚组以及I期肺腺癌中有效。我们发现它的预后能力是由涉及癌症干细胞和治疗耐药性的基因驱动的。总之，通过近似干性和肿瘤内异质性，信号熵为不同上皮性癌症提供了一个强有力的预后指标。癌症干细胞（CSC）假说认为，一小部分肿瘤细胞具有播种和生长肿瘤的能力，以及肿瘤内异质性，即单个患者肿瘤内癌细胞群的多样性，长期以来一直被认为是肿瘤学潜在预后指标的基础。然而，基于CSC表达特征的识别和肿瘤内异质性的测量，以临床相关的方式评估预后能力，目前提出了一个挑战。大多数提出的方法需要收集新的数据集，因此样本量有限，使其难以验证。这里我们考虑信号熵，信号通路混杂的度量，作为量化任何给定癌症样本的干性和异质性的一种手段，适用于公开可用的数据集。通过考虑来自乳腺癌和肺癌患者的5300多个原发肿瘤样本，我们在这里证明了信号熵提供了比其他主要临床预后指标更可靠和更普遍的预后指标。
The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. The Cancer Stem Cell (CSC) hypothesis, the idea that a small population of tumour cells have the capacity to seed and grow the tumour, and intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, have long been considered the basis of potential prognostic indicators in oncology. The identification of CSC based expression signatures and the measurement of intra-tumour heterogeneity, for an assessment of prognostic power in a clinically relevant manner, however, currently presents a challenge. Most proposed methodologies require the collection of new data sets and thus are limited in sample size, making them difficult to validate. Here we consider signalling entropy, a measure of signalling pathway promiscuity, as a means of quantifying the stemness and heterogeneity of any given cancer sample, applicable to publicly available data sets. By considering over 5300 primary tumour samples from both breast and lung cancer patients, we here demonstrate that signalling entropy provides a more robust and general prognostic measure than other leading clinical prognostic indicators.
登录
查看更多内容
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
50.3
作者：
Chin, Koei;DeVries, Sandy;Gray, Joe W.
通讯作者：
Gray, Joe W.
影响因子：
5.8
作者：
Ein-Dor, L;Kela, I;Domany, E
通讯作者：
Domany, E
影响因子：
64.8
作者：
Bedard PL;Hansen AR;Ratain MJ;Siu LL
通讯作者：
Siu LL
影响因子：
64.5
作者：
Chaffer CL;Marjanovic ND;Lee T;Bell G;Kleer CG;Reinhardt F;D'Alessio AC;Young RA;Weinberg RA
通讯作者：
Weinberg RA