Adam Julien, Sourisseau Tony, Olaussen Ken A, Robin Angélique, Zhu Chang Q, Templier Alexandre, Civet Alexandre, Girard Philippe, Lazar Vladimir, Validire Pierre, Tsao Ming S, Soria Jean-Charles, Besse Benjamin
Univ Paris-Sud, UMR-S981, Villejuif, France.
Gustave Roussy, DHU TORINO, Villejuif, France.
Cancer Biomark. 2016 Sep 26;17(3):323-333. doi: 10.3233/CBM-160644.
Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects.
One central quest in the field is therefore the identification of a predictive marker of the response to ACT.
We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort.
We identified MMS19, a component of the cytoplasmic Iron-Sulfur Assembly (CIA) machinery important for the Nucleotide Excision Repair (NER) pathway as a pivotal gene for cisplatin toxicity. We then confirmed the association between MMS19 expression and the response to Cisplatin treatment in a panel of NSCLC cell lines. Finally we validated these pre-clinical data in a subgroup of JBR.10 trial patients through a hypothesis-driven analysis, and showed that MMS19 levels associated with ACT benefit.
We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.
可切除的非小细胞肺癌（NSCLC）的治疗方案通常包括手术切除及辅助化疗（ACT）。然而，ACT的益处有限，且伴有严重的副作用。
因此，该领域的一个核心问题是确定ACT反应的预测标志物。
我们基于对来自发现患者队列的表达数据进行高内涵分析，采用了一种无偏倚的方法。
我们鉴定出MMS19，它是细胞质铁硫组装（CIA）机制的一个组成部分，对核苷酸切除修复（NER）途径很重要，是顺铂毒性的关键基因。然后，我们在一组NSCLC细胞系中证实了MMS19表达与顺铂治疗反应之间的关联。最后，我们通过假设驱动分析在JBR.10试验患者的一个亚组中验证了这些临床前数据，并表明MMS19水平与ACT益处相关。
因此，我们提出MMS19的表达水平作为可切除NSCLC患者ACT益处的候选预测标志物。
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