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Abstract A27: Expression of the EGFR suppressor LRIG1 is associated with survival in non-small cell lung cancer

Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is an endogenous inhibitor of epidermal growth factor receptor (EGFR) signaling, that is down-regulated in several forms of human cancer. The LRIG gene family also includes LRIG2 and LRIG3. EGFR signaling is important in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors are today considered standard treatment in patients with advanced disease. Since smoking recently was reported to down-regulate LRIG1 gene expression in lung epithelium and squamous cell carcinoma of the lung, the LRIG family of proteins may be important in lung cancer. The objective of the present study was to investigate if LRIG is a prognostic factor in non-small cell lung cancer (NSCLC). Therefore, we conducted an in silico analysis of LRIG gene expression in publicly available datasets using the Oncomine database and compared LRIG expression to clinical outcome. We also analyzed the LRIG protein expression by immunohistochemistry in a tissue micro array (TMA, n = 190) representing long- and short time survivors from a surgically treated NSCLC patient cohort. In seven out of 11 datasets in the in silico analysis, high expression of LRIG1 correlated (p<0.05) with long patient survival. This correlation was apparent both in adenocarcinoma and squamous cell carcinoma. In the TMA, LRIG1 expression was significantly higher in the long-term survival group than in the short time survival group (p<0.05). LRIG2 and LRIG3 protein expression did not significantly correlate to survival. In conclusion, both our in silico analysis of gene expression and TMA study of protein expression showed associations between high LRIG1 expression and longer NSCLC patient survival. This implicates that LRIG1 may be a prognostic factor in NSCLC and further studies on larger datasets have been initiated.