Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology.
Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology.
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透明细胞肾细胞癌基因表达的荟萃分析定义了一种变异子组，并鉴定了性别对肿瘤生物学的影响。
DOI：
10.1016/j.eururo.2011.10.007
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发表时间：
2012-02
期刊：
影响因子：
23.4
通讯作者：
Rathmell, W. Kimryn
中科院分区：
文献类型：
--
作者：
Brannon, A. Rose;Haake, Scott M.;Hacker, Kathryn E.;Pruthi, Raj S.;Wallen, Eric M.;Nielsen, Matthew E.;Rathmell, W. Kimryn
透明细胞肾细胞癌（ccRCC）显示分子和组织学异质性。以前描述的这种疾病的子集，ccA和ccB，是根据多基因表达谱定义的，但目前还不清楚这些亚组是否反映了疾病的全谱，或者这些分子亚型如何与组织学描述或性别相关。确定是否存在ccRCC的其他亚型，以及这些亚型是否与von Hippel-Lindau（VHL）失活、缺氧诱导因子（HIF）1和2表达、肿瘤组织学或性别相关。鉴定了六个大型的、公开可用的ccRCC基因表达数据库，其累积地提供了480个肿瘤的数据，用于通过元阵列编译进行元分析。在元阵列上进行无监督一致性聚类。检查肿瘤的多基因定义的一致亚型和VHL突变的表达特征与HIF状态、肿瘤组织学和性别的关系。观察到ccRCC的两个主要子集。然而，揭示了与野生型（WT）VHL表达谱和变异组织学的指征强烈相关的较小的第三簇。当去除变异组织学时，ccA肿瘤自然按性别划分。该技术受到持续批次效应、肿瘤采样偏倚和注释信息限制的潜在限制。ccRCC的ccA和ccB子集在组织学常规ccRCC肿瘤中的荟萃分析中是稳健的。第三组肿瘤被鉴定为可能代表ccRCC的新变体。在明确的透明细胞肿瘤中，性别可能会以这种方式描述肿瘤，它可能对当前的治疗和未来的药物开发产生影响。
Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development.
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