title: Potentials of plasma NGAL and MIC-1 as biomarker(s) in the diagnosis of lethal pancreatic cancer.
abstract: Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs.
authors: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors: Sukhwinder
authors: S
authors: Kaur
authors: Subhankar
authors: S
authors: Chakraborty
authors: Michael J
authors: MJ
authors: Baine
authors: Kavita
authors: K
authors: Mallya
authors: Lynette M
authors: LM
authors: Smith
authors: Aaron
authors: A
authors: Sasson
authors: Randall
authors: R
authors: Brand
authors: Sushovan
authors: S
authors: Guha
authors: Maneesh
authors: M
authors: Jain
authors: Uwe
authors: U
authors: Wittel
authors: Shailender K
authors: SK
authors: Singh
authors: Surinder K
authors: SK
authors: Batra
mesh_terms: D000209:Acute-Phase Proteins; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D018395:CA-19-9 Antigen / Q000097:blood; D003937:Diagnosis, Differential; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D016015:Logistic Models; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D050500:Pancreatitis, Chronic / Q000175:diagnosis; D011518:Proto-Oncogene Proteins / Q000097:blood; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D018395:CA-19-9 Antigen; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
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