Abstract
Prostate stem cell antigen was originally identified as an overexpressed gene in prostate cancer and its overexpression correlated with disease progression and prognosis. In this study, we investigated the clinical significance and therapeutic potential of prostate stem cell antigen expression in non-small cell lung cancer. Prostate stem cell antigen expression was examined by immunohistochemistry in 97 primary tumors and 21 metastatic lymph nodes from non-small cell lung cancer patients who underwent curative resection from January 2001 through March 2003. Therapeutic potential of targeting prostate stem cell antigen was further examined by small interfering RNA method using human lung cancer cell line (A549). Prostate stem cell antigen protein expression was detected in 94 of 97 primary lesions (97%) and all metastatic lymph nodes. Prostate stem cell antigen expression intensity was positively correlated with advanced pathological T-factor and stage (T1 vs. T2-4, P = 0.014; Stage I vs. Stages II-IV, P = 0.029, respectively). The prognosis of patients with low prostate stem cell antigen expression was significantly better than those with high prostate stem cell antigen expression (5-year disease-free survival rate; 90% vs. 53%, P = 0.001). Finally, small interfering RNA-mediated knockdown of prostate stem cell antigen resulted in the inhibition of lung cancer cell growth. Prostate stem cell antigen is highly expressed in non-small cell lung cancer and may be functionally important for this fatal disease.
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