MMS19 as a potential predictive marker of adjuvant chemotherapy benefit in resected non-small cell lung cancer

Abstract

Background: 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.

Objective: One central quest in the field is therefore the identification of a predictive marker of the response to ACT.

Methods: We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort.

Results: 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.

Conclusions: We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.

Keywords: DNA repair; Non-small-cell lung cancer; adjuvant chemotherapy.