Abstract 3020: Identification of a subgroup with good prognosis of small-cell lung cancer by miRNA expression profiling

Abstract

Abstract Background: Long-term outcomes of patients suffering from small-cell lung cancer (SCLC), a neuroendocrine carcinoma, are usually poor, but a few patients achieve long-term survival. Prognostic factors in SCLC have not been fully elucidated. Previously we successfully identified a neuroendocrine carcinoma subgroup with good prognosis by mRNA profiling (Jones et al. Lancet 2004). Here we attempted to identify the subgroup by microRNA (miRNA) profiling. miRNAs are known to negatively regulate gene expression and to be relevant to tumorigenesis, tumor classification and prognosis. Methods 63 samples (46 neuroendocrine tumors including 35 SCLC and 11 large cell neuroendocrine carcinomas (LCNEC), 5 squamous cell carcinoma (Sq), 4 adenocarcinoma and 8 normal lungs) were obtained through surgical resection. miRNA expression profiling was performed using miRNA microarray (Agilent). Hierarchical clustering was performed after selection of about 600 miRNA by choosing those with signal strength more than five. Results: Unsupervised hierarchical clustering using the 600 miRNA classified the tumors into two subgroups. Group 1 contained 20 SCLC (8 females and 12 males) and 3 LCNEC, and was associated with unfavorable prognosis. Group 2 contained 15 SCLC (1 female and 14 males), 8 LCNEC and 4 Sq, and was with good prognosis. 5-year survival of the two groups was 0% and 79%, respectively (p=0.007). As compared with our former study by mRNA, all 5 cases in the poor prognosis group fell into Group 1, and 6 out of 7 cases in the good prognosis group were included by Group 2, indicating good agreement between mRNA and miRNA profiling. Clinically, tumors of Group 1 tended to be smaller (29mm) than Group 2 (40mm), and cumulative smoking of Group 1 was lower (41 pack-years) than Group 2 (67 p-y) (p=0.03). Serum proGRP levels were significantly higher in Group 1 (50.9 pg/ml) than in Group 2 (26.4) (p<0.01). Among cases treated by preoperative chemotherapy (n=12), PR:NC ratio was 6:3 in Group 1 and 2:1 in Group 2, suggesting no apparent difference of chemosensitivity. A few miRNA were differentially expressed in the two groups. Conclusion: A distinct subgroup with favorable prognosis existed in SCLC. The subgroup was identified by both miRNA profiling as well as mRNA profiling. Detailed characterization of the subgroup will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3020.