Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer
Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer
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DOI：
10.1002/bjs.6683
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发表时间：
2009-10-01
影响因子：
9.6
通讯作者：
Kalady, M. F.
中科院分区：
文献类型：
--
作者：
Sanchez, J. A.;Krumroy, L.;Kalady, M. F.
背景：基于油微卫星不稳定性(MSI)、CpG岛甲基化表型(CIMP)以及KRAS和BRAF癌基因突变，已经提出了结直肠癌的分子分类。这项研究考察了这些分子类型的流行情况，以及在临床表现和结果方面的差异。方法：记录391例结直肠癌患者的人口学特征、肿瘤特征和生存率。分析肿瘤DNA的MSI(高(MSI-H)或微卫星稳定(MSS))、CIMP(高(CIMP-H)或NO(CIMP-neg))以及BRAF和KRAS突变。比较四种表型间的临床差异。大多数肿瘤为MSS/CIMP-neg(69.8%)，MSI-H/CIMP-H、MSI/CIMP-neg和MSS/CIMP-H型的分布几乎相等。MSS/CIMP-neg肿瘤低分化的可能性较小(P=0.009)。CIMP-H肿瘤在老年患者中更为常见(P<；0.001)。MSI-H/CIMP-H肿瘤具有较高的BRAF突变频率和较低的KRAS突变频率；而MSs/CIMP-neg肿瘤则相反(P<；0.001)。四种分子表型有分化生存的趋势(I-III期P=0.067)。MSI-H癌与较好的无瘤生存率相关(风险比为2.00(95%可信区间为1.03~3.91)；P=0.040)。这些不同的分子表型可能反映不同的预后。
Background: A molecular classification of colorectal cancer has been proposed based oil microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and Mutations ill the KRAS and BRAF oncogenes. This study examined the prevalence of these molecular classes, and differences ill clinical presentation and outcome.Methods: Demographics, tumour characteristics and survival were recorded for 391 subjects with colorectal cancer. Tumour DNA was analysed for MSI (high (MSI-H) or microsatellite stable (MSS)), CIMP (high (CIMP-H) or no (CIMP-neg))and BRAF and KRAS mutations. Clinical differences between four phenotypes were examined.Results. Most tumours were MSS/CIMP-neg (69.8 per cent), with a nearly equal distribution of MSI-H/CIMP-H, MSI/CIMP-neg and MSS/CIMP-H types. MSS/CIMP-neg tumours were less likely to be poorly differentiated (P = 0.009). CIMP-H tumours were more common in older patients (P < 0.001). MSI-H/CIMP-H tumours had a high frequency of BRAF mutation and a low rare of KRAS mutation; the opposite was true for MSS/CIMP-neg tumours (P < 0.001). The four molecular phenotypes tended towards divergent survival (P = 0.067 for stages I-III). MSI-H cancers were associated with better disease-free survival (hazard ratio 2.00 (95 per cent confidence interval 1.03 to 3.91); P = 0.040).Conclusion: Colorectal cancers are molecularly and clinically heterogeneous. These different molecular phenotypes may reflect variable prognosis.