Evidence for the importance of personalized molecular profiling in pancreatic cancer.
Evidence for the importance of personalized molecular profiling in pancreatic cancer.
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DOI：
10.1097/mpa.0000000000000020
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发表时间：
2014-03
期刊：
影响因子：
2.9
通讯作者：
McDonald JF
中科院分区：
文献类型：
--
作者：
Lili LN;Matyunina LV;Walker LD;Daneker GW;McDonald JF
补充数字内容可在文本中找到。越来越多的证据表明，靶向基因治疗对未来的癌症治疗有很大的希望。这种疗法的关键步骤是准确识别用于靶向治疗的适当候选基因/途径。一种方法是鉴定相对于对照受试者在患病个体组中显著富集的变异基因/途径。然而，如果同一种癌症有多个分子通路，则该疾病的分子决定因素在个体之间可能是异质的，并且可能未被组分析检测到。为了探索胰腺癌中的这个问题，我们比较了癌症和对照患者样本之间最显著差异表达的基因/途径，这些基因/途径通过组与个性化分析确定。我们发现，相对于通过个性化分析鉴定的基因/途径，通过使用组分析的基因表达谱鉴定的基因/途径之间几乎没有重叠。我们的研究结果表明，个性化的，而不是组的分子谱是最合适的方法，用于识别胰腺癌和其他可能具有异质性分子病因的癌症的靶向基因治疗的假定候选人。
Supplemental digital content is available in the text. There is a growing body of evidence that targeted gene therapy holds great promise for the future treatment of cancer. A crucial step in this therapy is the accurate identification of appropriate candidate genes/pathways for targeted treatment. One approach is to identify variant genes/pathways that are significantly enriched in groups of afflicted individuals relative to control subjects. However, if there are multiple molecular pathways to the same cancer, the molecular determinants of the disease may be heterogeneous among individuals and possibly go undetected by group analyses. In an effort to explore this question in pancreatic cancer, we compared the most significantly differentially expressed genes/pathways between cancer and control patient samples as determined by group versus personalized analyses. We found little to no overlap between genes/pathways identified by gene expression profiling using group analyses relative to those identified by personalized analyses. Our results indicate that personalized and not group molecular profiling is the most appropriate approach for the identification of putative candidates for targeted gene therapy of pancreatic and perhaps other cancers with heterogeneous molecular etiology.