Molecular phenotypes of colorectal cancer and potential clinical applications.
Molecular phenotypes of colorectal cancer and potential clinical applications.
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DOI：
10.1093/gastro/gov046
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发表时间：
2015-11
影响因子：
3.6
通讯作者：
Phipps AI
中科院分区：
文献类型：
--
作者：
Kocarnik JM;Shiovitz S;Phipps AI
结直肠癌(CRC)是一种异质性疾病，由多种可能的病因引起。这种异质性对结直肠癌的预后和临床治疗有重要意义。因此，结直肠癌风险和预后的流行病学研究--以及结直肠癌治疗的临床试验--必须对研究对象的结直肠肿瘤的分子表型敏感。在这篇综述中，我们描述了四种被广泛研究的反映结直肠癌异质性的肿瘤标志物：(I)微卫星不稳定性(MSI)或DNA错配修复(MMR)缺陷，(Ii)CpG岛甲基化表型(CIMP)，以及(Iii)BRAF和(Iv)KRAS的体细胞突变。这些肿瘤标志物已经被用来更好地描述结直肠癌的流行病学特征，并且越来越多地被用来指导临床决策。除了这些传统的肿瘤标记物外，我们还简要回顾了一些可能具有临床意义的新标记物。最后，认识到这些单独的肿瘤标记物都不是孤立的属性，而是更广泛的肿瘤表型的反映，我们回顾了一些假想的结直肠癌发生的病因途径及其相关的临床差异。
Colorectal cancer (CRC) is a heterogeneous disease, arising from many possible etiological pathways. This heterogeneity can have important implications for CRC prognosis and clinical management. Epidemiological studies of CRC risk and prognosis—as well as clinical trials for the treatment of CRC—must therefore be sensitive to the molecular phenotype of colorectal tumors in patients under study. In this review, we describe four tumor markers that have been widely studied as reflections of CRC heterogeneity: (i) microsatellite instability (MSI) or DNA mismatch repair (MMR) deficiency, (ii) the CpG island methylator phenotype (CIMP), and somatic mutations in (iii) BRAF and (iv) KRAS. These tumor markers have been used to better characterize CRC epidemiology and, increasingly, may be used to guide clinical decision-making. Going beyond these traditional tumor markers, we also briefly review some more novel markers likely to be of clinical significance. Lastly, recognizing that none of these individual tumor markers are isolated attributes but, rather, a reflection of broader tumor phenotypes, we review some of the hypothesized etiological pathways of CRC development and their associated clinical differences.