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.
Highlights
Despite decades of research, the prognosis for pancreatic cancer (PC) remains dismal, with an overall five-year survival rate of only about 5% [1]
We have previously reported that neutrophil gelatinase associated lipocalin (NGAL), a 24 kDa glycoprotein, is differentially upregulated during the progression of PC
Plasma samples from a total of 138 subjects were analyzed comprised of 91 PC (66%), Chronic pancreatitis (CP) (17%) and healthy control (HC, 17%) subjects
Summary
The prognosis for pancreatic cancer (PC) remains dismal, with an overall five-year survival rate of only about 5% [1]. Available techniques for the diagnosis of PC present several difficulties their invasive nature, need for specialized training, observer bias and the high cost to the healthcare system It has been demonstrated through experiments in animal models that molecular changes precede the appearance of changes in pancreatic architecture (detected by imaging techniques) [2]. There has been a growing emphasis on the identification of molecular markers that can identify PC at an early and potentially resectable stage Body fluids, such as blood, urine, bile and pancreatic juice represent a promising source of potential biomarkers. It was shown to be differentially expressed in PC tissues and elevated in the serum of PC patients compared to both healthy controls and those with benign pancreatic neoplasms [6]. Ozkan et al, observed significantly elevated expression of MIC-1 in PC cases in comparison to other pancreatobilary diseases and healthy controls. Serum MIC-1 was found to outperform CA19-9 in CA19-9, in differentiating patients with resectable pancreatic cancer from controls [8,9]
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