Cancer development and biology is influenced by the host immune system. Emerging data indicate that the context of immune cell infiltrates may contribute to cancer prognosis. However, the types of infiltrating immune cells that are critical for cancer development remain controversial. In attempts to gain insights into the immune networks that regulate and/or predict tumor progression, gene expression analysis was conducted on microarray datasets of resected tumor samples from 128 early-stage non-small cell lung cancer (NSCLC) adenocarcinoma patients. By limiting analysis to immune-related genes, we identified a 9-gene signature using MAximizing R Square Algorithm that selected for the greatest separation between favorable and adverse prognostic patient subgroups. The prognostic value of this 9-gene signature was validated in 10 additional independently published microarray datasets of lung adenocarcinoma [n = 1,097; overall survival hazard ratio (HR), 2.05; 95% confidence interval, 1.64-2.56; P < 0.0001] and was found to be an independent prognostic indicator relative to tumor stage (overall survival HR, 2.09, 95% confidence interval, 1.65-2.66; P < 0.0001). Network analysis revealed that genes associated with Fcε complex (FCER1, MS4A2) formed the largest and most significant pathway of the signature. Using immunohistochemistry, we validated that MS4A2, the β subunit of the IgE receptor expressed on mast cells, is a favorable prognostic indicator and show that MS4A2 gene expression is an independent prognostic marker for early-stage lung cancer patient survival. Cancer Immunol Res; 5(9); 821-9. ©2017 AACR.
©2017 American Association for Cancer Research.