Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer

作者：Karthik Suresh, Othello Del Rosario, Medha Kallem, Gayatri Singh, Anika Shah, Linda Zheng, Xin Yun, Nicolas Philip, Nirupama Putcha, Marni B. McClure, Haiyang Jiang, Franco R. D’Alessio, Meera Srivastava, Alakesh Bera, Larissa A. Shimoda, Michael L. Merchant, Madhavi J. Rane, Carolyn E. Machamer, Jason R. Mock, Robert S. Hagan, A.L. Koch, Naresh M. Punjabi, Todd M. Kolb, Mahendra Damarla · 发表于：Physiological Genomics · 年份：2023 · DOI：10.1152/physiolgenomics.00155.2022 · 被引用次数：8 · 研究领域：Cancer Mechanisms and Therapy、Cell death mechanisms and regulation、Lung Cancer Treatments and Mutations

) is required for caspase-3 nuclear translocation in the execution of apoptosis in endothelial cells. The objective was to determine MK2 expression in NSCLCs and the association between MK2 and clinical outcomes in patients with NSCLC. 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 and Kaplan-Meier curves. 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 2-yr 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 various cancers. This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.