Affiliations: [a] Univ Paris-Sud, UMR-S981, Villejuif, France | [b] Gustave Roussy, DHU TORINO, Villejuif, France | [c] INSERM, U981, Villejuif, France | [d] Princess Margaret Cancer Centre, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada | [e] Quinten, Paris, France | [f] Département Thoracique, Institut Mutualiste Montsouris, Paris, France | [g] Département d'Anatomie Pathologique, Institut Mutualiste Montsouris, Paris, France
Correspondence:
[*]
Corresponding author: Ken A. Olaussen, Univ Paris-Sud, UMR-S981, Villejuif, F-94805, France. E-mail:[email protected]
Note: [1] These authors contributed equally to this work.
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: Non-small-cell lung cancer, adjuvant chemotherapy, DNA repair
