Hierarchical clustering analysis of pathologic and molecular data identifies prognostically and biologically distinct groups of colorectal carcinomas
Hierarchical clustering analysis of pathologic and molecular data identifies prognostically and biologically distinct groups of colorectal carcinomas
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DOI：
10.1038/modpathol.2010.179
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发表时间：
2011-01-01
期刊：
影响因子：
7.5
通讯作者：
Carlo, Capella
中科院分区：
文献类型：
--
作者：
Furlan, Daniela;Carnevali, Ileana W.;Carlo, Capella
这项工作评估了基于结直肠癌的临床病理和分子特征相结合的形态分子分类的潜在优势。本文对126例散发性结直肠癌进行了非监督系统聚类分析，结合13个常规临床病理特征和Jass最近提出的5个分子标志物来区分散发性结直肠癌的4种分子亚型。生存分析采用COX比例风险模型。A、C组预后较好，B组预后较差(P=0.006)。A群和B群肿瘤的临床病理和分子特征分别与以微卫星不稳定和染色体不稳定为特征的结直肠癌特征高度一致。C组肿瘤的临床病理特征提示该疾病比B组肿瘤侵袭性小。在遗传学上，它们似乎介于A群和B群肿瘤之间，因为它们主要是微卫星稳定的肿瘤，表现出高水平的MGMT甲基化和杂合性丢失。C群肿瘤的染色体不稳定性显著低于B群肿瘤。更准确的肿瘤分类应该结合临床病理参数和分子生物标记物的预后能力，分子生物标志物提供有关癌症自然病史的信息。层次聚类对于进一步的翻译研究似乎是一个有用的、有前途的和强大的工具，应该引导我们为不同的癌症定义一个诊断和预后标志。《现代病理学》(2011年)24126137；doi：10.1038/modpathol.2010.179；2010年9月17日在线发布
This work has evaluated the potential superiority of a morphomolecular classification based on the combination of clinicopathologic and molecular features of colorectal cancers. A cohort of 126 colorectal carcinomas was investigated by unsupervised hierarchical clustering analysis to combine 13 routinely assessed clinicopathologic features and all five molecular markers recently suggested by Jass' classification to distinguish four molecular subtypes of sporadic colorectal carcinomas. Survival analysis was assessed by a Cox proportional hazards model. A clear separation into three prognostically significant groups was identified: cluster A and cluster C were associated with good prognosis and cluster B with poor prognosis (P=0.006). Clinicopathologic and molecular features of cluster A and cluster B tumors were strongly concordant with colorectal cancer profiles characterized by microsatellite instability or by chromosomal instability, respectively. The clinicopathologic features of cluster C tumors were suggestive of a less aggressive disease than cluster B tumors. Genetically, they appeared intermediate between cluster A and cluster B tumors, as they were mainly microsatellite stable tumors showing high levels of both MGMT methylation and loss of heterozygosity. Chromosomal instability was significantly lower in cluster C than in cluster B tumors. A more accurate tumor classification should combine the prognostic power of clinicopathologic parameters with molecular biomarkers that provide information regarding the natural history of the cancer. Hierarchical clustering seems to be a useful, promising and powerful tool for further translational studies and should lead us to define a diagnostic and prognostic signature for different carcinomas. Modern Pathology (2011) 24, 126-137; doi:10.1038/modpathol.2010.179; published online 17 September 2010