Combined use of CEMIP and CA 19-9 enhances diagnostic accuracy for pancreatic cancer

Abstract

Carbohydrate antigen (CA) 19-9 is the only diagnostic marker used in pancreatic cancer despite its limitations. Here, we aimed to identify the diagnostic role of CEMIP (also called KIAA1199) combined with CA 19-9 in patients with pancreatic cancer. A retrospective analysis of prospectively collected patient samples was performed to determine the benefit of diagnostic markers in the diagnosis of pancreatic cancer. We investigated CEMIP and CA 19-9 levels in 324 patients with pancreatic cancer and 49 normal controls using serum enzyme-linked immunosorbent assay. Median CA 19-9 and CEMIP levels were 410.5 U/ml (40.8-3342.5) and 0.67 ng/ml (0.40-1.08), respectively, in patients with pancreatic cancer. The AUROC for CA 19-9 and CEMIP were 0.847 (95% confidence interval [CI]: 0.806-0.888) and 0.760 (95% CI: 0.689-0.831), respectively. Combination of CA 19-9 with CEMIP showed markedly improved AUROC over CA 19-9 alone in pancreatic cancer diagnosis (0.94 vs. 0.89; P < 0.0001). CEMIP showed a diagnostic yield of 86.1% (68/79) in CA 19-9 negative pancreatic cancer. Combined use with CEMIP showed significantly improved diagnostic value compared with CA 19-9 alone in pancreatic cancer. Especially, CEMIP may be a complementary marker in pancreatic cancer patients with normal CA 19-9 levels.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Summary of serum CEMIP expression levels detected from pancreatic cancer patients and individuals without cancer. The CEMIP expression was significantly higher in patients with pancreatic cancer than in individuals without cancer (P 

Figure 2

ROC curves of CEMIP, CA 19-9, and both to diagnose pancreatic cancer. Normal individuals were defined as people who were not diagnosed with pancreatic cancer and were divided into two groups (healthy individuals and patients with benign disease). (A) Normal individuals including healthy individuals and patients with benign disease were the control group. Combination with CEMIP showed markedly improved AUROC over that of CA 19-9 alone in the diagnosis of pancreatic cancer against normal individuals (AUROC, 0.89 vs. 0.85; P = 0.0119). (B) Healthy individuals were the control group. Combination with CEMIP showed markedly improved AUROC over that of CA 19-9 alone in the diagnosis of pancreatic cancer against healthy individuals (AUROC, 0.94 vs. 0.89; P < 0.0001). CEMIP, cell migration-inducing hyaluronan binding protein; CA 19-9, carbohydrate antigen 19-9; ROC, receiver operating characteristic; AUC, area under the ROC curve.

Figure 3

Distribution of CEMIP and CA 19-9 levels in patients diagnosed with pancreatic cancer. The optimal cut-off levels of CA 19-9 and CEMIP were 37 U/mL and 0.218 ng/ml, respectively. A total of 68 CA 19-9 negative patients (black colored circle) were diagnosed using CEMIP (diagnostic yield, 86.1%). CEMIP, cell migration-inducing hyaluronan binding protein; CA 19-9, carbohydrate antigen 19-9.

Figure 4

Correlation between CEMIP and survival in patients with pancreatic cancer using Kaplan-Meier curve. Low CEMIP levels were significantly associated with longer overall survival (median overall survival, 13.7 vs. 9.8 months, P = 0.0175). CEMIP, cell migration-inducing hyaluronan binding protein.