Molecular subtyping for clinically defined breast cancer subgroups.
Molecular subtyping for clinically defined breast cancer subgroups.
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DOI：
10.1186/s13058-015-0520-4
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发表时间：
2015-02-26
期刊：
影响因子：
--
通讯作者：
Plevritis S
中科院分区：
文献类型：
--
作者：
Zhao X;Rødland EA;Tibshirani R;Plevritis S
乳腺癌通常分为内在分子亚型。标准基因定中心通常在分子分型之前进行，但当研究队列中临床病理特征的分布与用于获得分类器的训练队列的分布不同时，它可能产生不准确的分类。我们提出了一个亚组特异性基因中心的方法进行分子分型的研究队列，具有相对于训练队列的临床病理特征的偏态分布。在这样的研究队列中，我们将每个基因集中在指定的百分位数上，其中百分位数是从具有与研究队列相似的临床病理学特征的训练队列的亚组中确定的。我们使用PAM 50分类器及其相关的北卡罗来纳州大学（University of North Carolina）训练队列来演示我们的方法。我们考虑了具有偏斜临床病理学特征的研究队列，包括由UNC-PAM 50训练队列的单一原型亚型（n = 139）、外部雌激素受体（ER）阳性队列（n = 48）和外部三阴性队列（n = 77）组成的亚组。当应用于PAM 50训练队列的原型肿瘤子集时，亚组特异性基因定中心提高了预测性能，准确度在77%至100%之间，而标准基因定中心的准确度在17%至33%之间。它降低了PAM 50训练队列中ER阳性（11%对28%; P = 0.0389）、ER阴性（5%对41%; P < 0.0001）和三阴性（11%对56%; P = 0.1336）亚组的分类错误率。此外，对于由不同比例的ER阳性与ER阴性病例组成的亚型分型研究队列，它产生了更高的准确性。最后，它增加了外部ER阳性队列中分配的管腔亚型和外部三阴性队列中分配的基底样亚型的百分比。基因定中心通常是准确应用分子亚型分类器所必需的。与标准基因定中心相比，我们提出的亚组特异性基因定中心在临床病理特征相对于训练队列倾斜的研究队列中产生了更准确的分子亚型分配。本文的在线版本（doi：10.1186/s13058-015-0520-4）包含补充材料，可供授权用户使用。
Breast cancer is commonly classified into intrinsic molecular subtypes. Standard gene centering is routinely done prior to molecular subtyping, but it can produce inaccurate classifications when the distribution of clinicopathological characteristics in the study cohort differs from that of the training cohort used to derive the classifier. We propose a subgroup-specific gene-centering method to perform molecular subtyping on a study cohort that has a skewed distribution of clinicopathological characteristics relative to the training cohort. On such a study cohort, we center each gene on a specified percentile, where the percentile is determined from a subgroup of the training cohort with clinicopathological characteristics similar to the study cohort. We demonstrate our method using the PAM50 classifier and its associated University of North Carolina (UNC) training cohort. We considered study cohorts with skewed clinicopathological characteristics, including subgroups composed of a single prototypic subtype of the UNC-PAM50 training cohort (n = 139), an external estrogen receptor (ER)-positive cohort (n = 48) and an external triple-negative cohort (n = 77). Subgroup-specific gene centering improved prediction performance with the accuracies between 77% and 100%, compared to accuracies between 17% and 33% from standard gene centering, when applied to the prototypic tumor subsets of the PAM50 training cohort. It reduced classification error rates on the ER-positive (11% versus 28%; P = 0.0389), the ER-negative (5% versus 41%; P < 0.0001) and the triple-negative (11% versus 56%; P = 0.1336) subgroups of the PAM50 training cohort. In addition, it produced higher accuracy for subtyping study cohorts composed of varying proportions of ER-positive versus ER-negative cases. Finally, it increased the percentage of assigned luminal subtypes on the external ER-positive cohort and basal-like subtype on the external triple-negative cohort. Gene centering is often necessary to accurately apply a molecular subtype classifier. Compared with standard gene centering, our proposed subgroup-specific gene centering produced more accurate molecular subtype assignments in a study cohort with skewed clinicopathological characteristics relative to the training cohort. The online version of this article (doi:10.1186/s13058-015-0520-4) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Borgan E;Sitter B;Lingjærde OC;Johnsen H;Lundgren S;Bathen TF;Sørlie T;Børresen-Dale AL;Gribbestad IS
通讯作者：
Gribbestad IS
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS
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
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D
DOI：
10.1186/bcr1399
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Perreard L;Fan C;Quackenbush JF;Mullins M;Gauthier NP;Nelson E;Mone M;Hansen H;Buys SS;Rasmussen K;Orrico AR;Dreher D;Walters R;Parker J;Hu Z;He X;Palazzo JP;Olopade OI;Szabo A;Perou CM;Bernard PS
通讯作者：
Bernard PS