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RATIONALE Non-small cell lung cancers (NSCLC) demonstrate intrinsic resistance to cell death, even after chemotherapy. Previous work suggested defective nuclear translocation of active caspase-3 in observed resistance to cell death. We have identified mitogen activated protein kinase activated protein kinase 2(MK2) is required for caspase-3 nuclear translocation in the execution of apoptosis in endothelial cells. OBJECTIVE To determine MK2 expression in NSCLCs and the association between MK2 and clinical outcomes in NSCLC patients. METHODS Clinical and MK2 mRNA data were extracted from two demographically distinct NSCLC clinical cohorts, North American (The Cancer Genome Atlas, TCGA) and East Asian (EA). Tumor responses following first round of chemotherapy were dichotomized as Clinical Response (complete response, partial response and stable disease) or Progression of Disease. Multivariable survival analyses were performed using Cox proportional hazard ratios, logistic regression odd ratios and Kaplan-Meier curves. RESULTS NSCLC exhibited lower MK2 expression than SCLC cell lines. In patients, lower tumor MK2 transcript levels were observed in those presenting with late-stage NSCLC. Higher MK2 expression was associated with clinical response following initial chemotherapy and independently associated with improved two-year survival in two distinct cohorts, 0.52(0.28-0.98) and 0.1(0.01-0.81), TCGA and EA respectively, even after adjusting for common oncogenic driver mutations. Survival benefit of higher MK2 expression was unique to lung adenocarcinoma when comparing across cancers. CONCLUSION This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.