Protein Induced by Vitamin K Absence II: A Potential Biomarker to Differentiate Pancreatic Ductal Adenocarcinoma from Pancreatic Benign Lesions and Predict Vascular Invasion

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal tumor with a poor prognosis. Serum biomarker carbohydrate antigen 19-9 (CA19-9) was the only well-established biomarker for PDAC with inadequate efficacy. This present study aimed to determine the ability of PIVKA-II to discriminate PDAC from pancreatic benign lesions and predict vascular invasion preoperatively.

Methods: Patients who underwent pancreatic surgery from 2017 to 2020 were enrolled. We examined the differential diagnostic ability of protein induced by vitamin K absence II (PIVKA-II), CA19-9, and their combination and 138 with PDAC evaluated the predictive value of PIVKA-II for vascular invasion in PDAC.

Methods: A total of 138 patients with PDAC and 90 patients with pancreatic benign lesions who underwent pancreatic surgery from 2017 to 2020 were enrolled. The clinicopathological characteristics were recorded.

Results: There was a significant difference in levels of serum PIVKA-II between PDAC patients and patients with pancreatic benign lesions (p < 0.001). When the cut-off value was set to 28.9 mAU/mL according to the ROCs, the AUC, sensitivity, and specificity of PIVKA-II were 0.787, 68.1%, and 83.3%, respectively. The combined PIVKA-II and carbohydrate antigen 19-9 (CA19-9) enhanced the diagnostic accuracy, and the AUC, sensitivity, and specificity were 0.945, 87.7%, and 94.4%, respectively. PIVKA-II > 36.4 mAU/mL were independent predictive factors of vascular invasion in PDAC (p < 0.001).

Conclusion: PIVKA-II was a potential diagnostic biomarker to differentiate PDAC from pancreatic benign lesions. PIVKA-II was complementary to CA19-9, and the combination enhanced the differential diagnostic performance. PIVKA-II > 36.4 mAU/mL was an independent predictive factor of vascular invasion in PDAC.

Keywords: biomarker; diagnosis; pancreatic cancer; protein induced by vitamin K absence II; vascular invasion.

Figure 1

Flowchart of case selection in this study. PDAC, pancreatic ductal adenocarcinoma; CA19-9, carbohydrate antigen 19–9; PIVKA-II, protein induced by vitamin K absence-II.

Figure 2

A comparison of serum protein induced by vitamin K absence-II (PIVKA-II) levels in patients with pancreatic ductal adenocarcinoma and benign lesions.

Figure 3

ROC curves for pancreatic ductal adenocarcinoma diagnosis. (1) ROC curve of PIVKA-II for PDAC diagnosis; (2) ROC curve of CA19-9 for PDAC diagnosis; (3) ROC curve of PIVKA-II/Total bilirubin for PDAC diagnosis. ROC, Receiver operating characteristics; PIVKA-II, protein induced by vitamin K absence-II, CA19-9, carbohydrate antigen 19-9; AUC, the area under the curve; PDAC, pancreatic ductal adenocarcinoma.

Figure 4

ROC curves of CA19-9, PIVKA-II, and their combination for distinguishing pancreatic ductal adenocarcinoma. ROC, Receiver operating characteristics; PIVKA-II, protein induced by vitamin K absence-II; CA19-9, carbohydrate antigen 19–9.

Figure 5

Cut-off values of PIVKA-II, CA19-9, and tumor size for predicting vascular invasion in pancreatic ductal adenocarcinoma. CA19-9 levels had no significant difference between patients with and without vascular invasion (p = 0.47). The ROCs showed the cut-off value of CA19-9 was 198.5 U/L, and the AUC was 0.54 (95% CI, 0.44–0.63). PIVKA-II levels significantly differed between patients with and without vascular invasion (p < 0.0001). The ROCs showed the cut-off value of PIVKA-II was 36.4 mAU/mL, and the AUC was 0.76 (95% CI, 0.68–0.84). Tumor size had no significant difference between patients with and without vascular invasion (p = 0.72). The ROCs showed the cut-off value of maximum tumor size was 7.8 cm, and the AUC was 0.48 (95% CI, 0.39–0.58). AUC is the area under the curve; ROC is receiver operating characteristics; CI is confidence interval; PIVKA-II is protein induced by vitamin K absence-II; CA19-9 is carbohydrate antigen 19-9.

Figure 6

Diagnostic efficacy of PIVKA-II, CT examination and their combination for vascular invasion in PDAC. When we evaluate the diagnostic efficacy of combined CT examination and PIVKA-II for vascular invasion in PDAC, single positive was defined as positive and double negative was defined as negative. PIVKA-II, Protein induced by vitamin K absence-II; CT, computed tomography; PDAC, pancreatic ductal adenocarcinoma.