Kupert et al. BMC Cancer 2011, 11:513 http://www.biomedcentral.com/1471-2407/11/513 Page 4 of 10 Table 2 Plasma sPLA2-IIa levels and diagnosis in patients with benign SPNs from BNLCC Sample sPLA2-IIa (pg/ml) Diagnosis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 1039.2 1589.2 480.83 8980.8 1030.8 1105.8 3680.8 922.5 797.5 2372.5 1789.2 580.83 2305.8 872.5 2714.2 714.17 2105.8 2422.17 1226.52 2217.83 1804.78 430.87 3878.7 835.22 572.5 1553.75 816.25 1328.75 1228.13 0.9 cm nodule and heavy smoker 1.3 × 1.4 × 1.1 cm subpleural nodule, necrotizing granuloma Nodule 2 cm Necrotizing granulomatous Nonnecrotizing granulomas Abscess colonized with fungal hyphae Nodule with organizing pneumonia pattern of lung injury Caseating granulomas with emphysematous changes Nodules of caseating granulomas Necrotizing granuloma with fungal organisms Peribronchial tumorlet-2 mm and focal parenchymal fibrosis Necrotizing granuloma with fungal organisms Necrotizing granuloma (2 × 1.7 × 1.3 cm) Broncial and broncheolar ectasis with fibrosis and chronic inflammation c/w bronchiectasis Bronchiolitis obliterans organizing pneumonia Focal fibrosis and chronic inflammation and reactive pneumocyte hyperplasia Caseating granulomas with fungal elements Myolipomatous polyp Active granulomatous inflammation and possible sarcoidosis Neurofibroma, 4.5 × 3.5 cm Active non-caseating granulomas Necrotizing granuloma with fungal organisms Caseating necrotizing granulomas with fungal elements Non-caseating granulomas with fungal elements Necrotizing granulomatous inflammation with fungal organisms consistent with Aspergillus Necrotizing granulomas with fungal yeast forms consistent with Histoplasma Organizing suppurative bronchopneumonia with pleural adhesions Presented with sTable lung nodule necrotizing granuloma and Langerhans’ cell histiocytosis *The data in bold is higher than the cutoff value of the blood test. IIa were also associated with a decreased overall survival (Unpaired t test with Welch correction: P = 0.0457) (see Additional file 1). The mean overall survival year for high sPLA2-IIa (> 2.4 ng/ml, n = 6) was 1.8 ± 1.3 years, while the mean overall survival year for low sPLA2-IIa (< 2.4 ng/ml, n = 11) was 3.3 ± 1.9 years. Given the heterogeneous nature of cancer, the com- bined blood tests including a panel of biomarkers will increase the sensitivity for cancer prediction. Carci- noembryonic Antigen (CEA) and Cytokeratin-19 frag- ment (Cyfra 21.1) with the optimum cutoff value 6 ng/ ml and 3.3 ng/ml, respectively, are two best biomarkers for predicting NSCLC currently under investigation [12,26,27]. Positive prediction for the presence of lung cancer by the combined blood tests was defined as one or more biomarkers higher than their cutoff values. We found that a combination of sPLA2-IIa (2.4 ng/ml cutoff value), Cyfra 21.1 (3.3 ng/ml cutoff value), and CEA (6 ng/ml cutoff value) tests increased the sensitivity for lung cancer prediction up to 62% from 48% by sPLA2- IIa test alone for 96 cancers relative to 29 patients with benign SPNs from the BNLCC (Table 3b and see Addi- tional file 1 and 4). Furthermore, the combined tests increased the sensitivity for lung cancer prediction up to 59% and 72% from 45% and 67% by sPLA2-IIa test alone for 44 T1 stage cancers and 18 T2 stage cancers relative to 29 patients with benign SPNs, respectively. CEA and Cyfra 21.1 test alone had only 20% and 14% sensitivity, respectively (Table 3b). Among the 5 patients with benign lung nodules and higher level of plasma sPLA2-IIa than the cutoff value 2.4 ng/ml, two patient suffered from localized pneumo- nia, one patient suffered from myolipomatous polyp, and the other two patients were diagnosed with