A Seven-Gene Signature Aggregates a Subgroup of Stage II Colon Cancers with Stage III
A Seven-Gene Signature Aggregates a Subgroup of Stage II Colon Cancers with Stage III
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DOI：
10.1089/omi.2012.0039
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Olschwang, Sylviane
中科院分区：
文献类型：
--
作者：
Laibe, Sophy;Lagarde, Arnaud;Olschwang, Sylviane
结直肠癌是世界上最常见的癌症之一。组织学分期是有效的，但结合分子标记物可能会改善肿瘤分类。基因表达谱已被定义为II期和III期肿瘤的预后预测因子，但其在医疗实践中的应用仍存在争议。II期肿瘤被认为是一个异质性组，高风险的形态学特征已被用来证明辅助化疗。我们建议在这里调查的临床特征和表达谱从第二阶段和第三阶段结肠癌没有DNA错配修复缺陷。获得两个系列的130和66个结肠癌样品。在寡核苷酸微阵列上建立表达谱，并在R/Bioconductor环境中处理。分层，然后监督，分析连续进行应用数据采样方法。发现7个基因的分子标记聚集III期肿瘤，调整后的p值低于10（-10）。在两个系列中，II期肿瘤的亚组聚集了该簇。没有发现与疾病严重程度的相关性，但区分基因的功能表明，肿瘤已根据其对辅助靶向或经典疗法的假定反应进行了分类。进一步的药物遗传学研究可能会证实这一观察结果。
Colorectal cancer is one of the most common cancers in the world. Histological staging is efficient, but combination with molecular markers may improve tumor classification. Gene expression profiles have been defined as prognosis predictors among stage II and III tumors, but their implementation in medical practice remains controversial. Stage II tumors have been recognized as a heterogeneous group, and high-risk morphologic features have been used to justify adjuvant chemotherapy. We propose here the investigation of clinical features and expression profiles from stage II and stage III colon carcinomas without DNA mismatch repair defects. Two series of 130 and 66 colon cancer samples were obtained. Expression profiles were established on oligonucleotide microarrays and processed in the R/Bioconductor environment. Hierarchical, then supervised, analyses were successively performed by applying a data-sampling approach. A molecular signature of seven genes was found to cluster stage III tumors with adjusted p values lower than 10(-10). A subgroup of stage II tumors aggregated this cluster in both series. No correlation was found with disease severity, but the function of the discriminating genes suggests that tumors have been classified according to their putative response to adjuvant targeted or classic therapies. Further pharmacogenetic studies might verify this observation.