ARTICLE ABSTRACTPurpose: This study aims to identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies for lung cancer.Experimental Design: We screened for genes that were highly transactivated in a large proportion of 120 lung cancers by means of a cDNA microarray representing 27,648 genes and found chondrolectin (CHODL) as a candidate. Tumor tissue microarray was applied to examine the expression of CHODL protein and its clinicopathologic significance in archival non–small cell lung cancer (NSCLC) tissues from 295 patients. A role of CHODL in cancer cell growth and/or survival was examined by siRNA experiments. Cellular invasive effect of CHODL on mammalian cells was examined by Matrigel assays.Results: Immunohistochemical staining revealed that strong positivity of CHODL protein was associated with shorter survival of patients with NSCLC (P = 0.0006), and multivariate analysis confirmed it to be an independent prognostic factor. Treatment of lung cancer cells with siRNAs against CHODL suppressed growth of the cancer cells. Furthermore, induction of exogenous expression of CHODL conferred growth and invasive activity of mammalian cells.Conclusions: CHODL is likely to be a prognostic biomarker in the clinic and targeting CHODL might be a strategy for the development of anticancer drugs. Clin Cancer Res; 17(24); 7712–22. ©2011 AACR.