Development of serum parameters panels for the early detection of pancreatic cancer

Abstract

Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross-validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19-9, albumin (ALB), C-reactive protein (CRP) and interleukin (IL)28 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all-stage, 96.10% for early-stage and 98.80% for advanced-stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non-PDAC. The panel consisting of CA19-9, carbon dioxide, CRP and IL-6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all-stage, 75.30% for early-stage and 74.40% for advanced-stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.Pancreatic cancer is the fourth leading cause of cancer death in the United States. In 2012, an estimated 43,920 people were diagnosed with pancreatic cancer, with an estimated 37,390 deaths. 1 Pancreatic ductal adenocarcinoma (PDAC) is the most common type and constitutes about 90% of all pancreatic cancer patients. Despite considerable advances in the treatment of many other human tumors, the 5-year survival rate of PDAC had not changed much in the past several

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

“…In the present study, we found that levels of the serum marker of acute inflammation (CRP) and an inflammatory mediator (TNFSF13) were significantly higher in patients with PDAC-DM than in those without diabetes and in pancreatitis patients. Though the serum levels of CRP and TNFSF13 in patients with PDAC-DM were not directly compared with those of healthy individuals in our study, the serum CRP and TNFSF13 levels in patients with chronic pancreatitis were shown to be slightly higher and the same as those of healthy individuals, respectively [18][19][20]. Our data demonstrated similar levels of CRP mRNA expression in tissues from patients with and without PDAC-DM, and in patients with chronic pancreatitis, excluding the possibility that PDAC lesions are the source of the elevated CRP in the serum of patients with PDAC-DM.…”

Tumor‐driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL‐8

“…In addition, many of experimental studies have characterized that there was higher serum level of IL-8 in patients with PDAC compared to healthy controls, suggesting the diagnostic potential as novel clinical marker of PDAC patients. 40,41 In conclusion, the present study represented a reciprocal relationship between PDAC cells and tumor-driven like macrophages. As a multifunction chemokine, IL-8 in our study was just investigated its effect on EMT switch in PDAC cells, and hence further exploration will certainly be necessary to figure out its other effect on cancer stem cell, angiogenesis, and chemoresistance.…”

Comparison of the tumor cell secretome and patient sera for an accurate serum-based diagnosis of pancreatic ductal adenocarcinoma

“…Some of the proteins, such as IL10, ID1 and IL2, had been implicated as possible biomarkers of pancreatic cancer before [41–43]. However, the result sheds new light on the process by which marker molecules should be selected for a useful diagnostic signature.…”