Abstract LB-212: Elevated plasma NGAL and MIC-1 are novel biomarkers for the diagnosis of pancreatic adenocarcinoma

Abstract

Abstract Pancreatic cancer (PC) is a highly lethal malignancy (5-year survival <5%). The secretory glycoproteins neutrophil gelatinase associated lipocalin (NGAL) and macrophage inhibitory cytokine-1 (MIC-1) have both been shown to be involved in the pathogenesis of PC. We hypothesized that plasma NGAL and MIC-1 levels are elevated in patients with PC and could be useful in the diagnosis of PC either alone or in combination with CA19-9. To investigate this hypothesis, we analyzed NGAL, MIC-1 and CA19-9 levels in plasma samples from patients with PC (n=145, 66 pre-operative and 79 postoperative samples) and compared it with that in healthy individuals (n=27). NGAL and MIC-1 levels were measured using ELISA while CA19-9 levels were analyzed by radioimmunoassay. The mean plasma NGAL, MIC-1 and CA19-9 levels in pre-operative PC patients were 141 ± 17.5 ng/nl, 59±32.4 ng/ml and 988±449.5 U/ml which was higher than their corresponding levels in the healthy controls (74.5±3 ng/ml (p=0.0004), 7±2.7 ng/ml (p=0.11) and 35±2.7 U/ml (p<0.00001) for NGAL, MIC-1 and CA19-9, respectively). At a cut-off of >90ng/ml, NGAL was 67% sensitive (95% C.I. 60%-80%) and 93% specific (95% C.I. 76%-99%) in distinguishing PC from controls. In comparison, CA19-9 at a cut-off of >37U/ml was 82% sensitive (95% C.I. 73%-89%) and 67% specific (95% C.I. 46%-83%) while MIC-1 at a level >1.85 ng/ml had a sensitivity of 82% (95% C.I. 73%-89%) and specificity of 63% (95% C.I. 42%-80%). Neither NGAL nor MIC-1 levels differed significantly between PC patients with resectable vs unresectable tumors (p=0.54 and 0.37), male vs. female (p=0.92 and 0.11), by histological grade (p=0.26 and 0.29), location of tumor (p=0.58 and 0.96) or among those with or without a concomitant diagnosis of type 2 diabetes (p=0.46 and 0.50 respectively). However, NGAL (but not MIC-1) levels were significantly higher in PC patients above 65 yrs of age (177.1±30 ng/ml compared to 97±8.6 ng/ml in those ≤ 65 yrs old, p=0.017) and lower in post-operative compared to pre-operative PC patients (106±7 ng/ml vs. 138±15 ng/ml respectively, p=0.057). Applying a criterion of positivity of at least one of the three markers improved the sensitivity of diagnosing PC to 98.5%, while positivity for any two markers (NGAL or CA19-9, MIC-1 or CA19-9 and NGAL or MIC-1) was less sensitive in diagnosing PC (92%, 97% and 91% sensitive respectively). The highest specificity was obtained when both NGAL and CA19-9 were above their cut-offs (96%). Adding MIC-1 to this did not improve specificity. Twelve pre-operative PC patients had CA19-9<37U/ml. 58% (n=7) of these patients had NGAL levels above the cut-off compared to 83% (n=10) for MIC-1. Using a criterion of either NGAL or MIC-1 positivity in these patients correctly identified 92% (n=11) PC patients who were negative for CA19-9. In summary, we have identified NGAL as a highly specific marker of PC compared to CA19-9. Further, a combination of NGAL, MIC-1 and CA19-9 was more sensitive than either marker alone in diagnosing PC, while a combination of CA19-9 and NGAL gave the highest specificity. A combination of NGAL and MIC-1 was useful to identify PC patients who were negative for CA19-9. Our results suggest a potential role for NGAL and MIC-1 in the diagnosis of PC, especially in patients who do not express CA19-9. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-212.