Evaluations of the combined use of blood- and tissue-based protein biomarkers for pancreatic cancer.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a low 5-year survival rate. Biomarkers may be of value for the early diagnosis of pancreatic cancer. This study assessed blood- and tumour tissue-based biomarkers associated with pancreatic cancer. We studied 61 patients who underwent pancreatic resection. Of these 61 patients, 46 patients had PDAC, and 15 patients had inflammatory tumours. Blood and tumour tissue levels of VEGF, hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) were measured. Blood concentrations of VEGF (p < 0.000001) and HIF-1α (p = 0.000002) were significantly higher in the PDAC group than in the inflammatory tumour group. Tumour tissue concentrations of VEGF (p < 0.000001), HIF-1α (p = 0.000005) and GLUT1 (0.000002) were also significantly higher in the PDAC group. Univariate analyses revealed that age, BMI, and blood levels of CA19-9, VEGF, and HIF-1α were potential predictors of PDAC. Potential predictors of PDAC in tumour tissue were VEGF, HIF-1α and GLUT1. Multivariate analyses found that VEGF was the most powerful independent predictor of PDAC in blood (OR = 1.016; 95% CI: 1.007-1.025; 0.001) and tumour tissue (OR = 1.02; 95% CI: 1.008-1.032, p = 0.001). The cut-off point for blood VEGF was 134.56 pg/ml, with a sensitivity of 97.8%, specificity of 86.7%, PPV of 95.7%, and NPV of 92.9%. The cut-off point for tissue tumour VEGF in PDAC was 208.59 pg/mg, with a sensitivity, specificity, PPV and NPV of 97.7%, 92.9%, 97.7%, and 92.9%, respectively. There are significant differences in blood-based biomarkers for differentiating between PDAC and inflammatory tumours of the pancreas. VEGF was an independent predictor of PDAC independent of its addition to the routinely used tumour marker CA19-9 antigen.