The Prospect of Improving Pancreatic Cancer Diagnostic Capabilities by Implementing Blood Biomarkers: A Study of Evaluating Properties of a Single IL-8 and in Conjunction with CA19-9, CEA, and CEACAM6

Abstract

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan-Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities.

Keywords: IL-8; chronic pancreatitis; diagnostic biomarker; obstructive jaundice; pancreatic cancer.

Figure 1

(a) Boxplot of IL-8 serum levels for the control group, patients with PDAC and CP. (b) Box plot of IL-8 serum levels among different PDAC stages (B). IL-8—Interleukin 8. PDAC—Pancreatic ductal adenocarcinoma. CP—Chronic pancreatitis. *— represent potential outliers.

Figure 2

ROC curve analysis of IL-8 serum concentrations in patients with PDAC and control group or CP: (a) ROC curve of IL-8 (PDAC and control group); (b) ROC curve of IL-8 (PDAC and CP); (c) Specificity and sensitivity regarding serum IL-8 concentration (PDAC and control group); (d) Specificity and sensitivity in regarding serum IL-8 concentration (PDAC and CP); (e) J regarding serum IL-8 concentration (PDAC and control group); (f) J regarding serum IL-8 concentration (PDAC and CP); (g) ROC curve of all four biomarkers combined (PDAC and control group); (h) ROC curve of all four biomarkers combined (PDAC and CP). IL-8—Interleukin 8. J—Youden index. PDAC—Pancreatic ductal adenocarcinoma. CP—Chronic pancreatitis.

Figure 3

Forest plot showing the area under the biomarkers combinations efficiency curve in separate groups. In addition to the analysis, possible sensitivity and specificity were calculated for each biomarker’s combinations. IL-8—Interleukin 8; CEACAM6—Carcinoembryonic antigen cell adhesion molecule 6; CEA—Carcinoembryonic antigen; CA19-9—Carbohydrate antigen 19-9; PDAC—Pancreatic ductal adenocarcinoma; CP—Chronic pancreatitis; AUC—Area under the ROC curve; CI—Confidence interval; p-value—Statistical significance was set at a p-value of less than 0.05.