Validation of IL-7R as an Immunological Biomarker for Human Pancreatic Ductal Adenocarcinoma

Abstract

Simple Summary Despite being the fourth-leading cause of cancer-related deaths worldwide, pancreatic ductal adenocarcinoma (PDAC) lacks early diagnostic methods. We performed mRNA sequencing on peripheral blood mononuclear cells isolated from PDAC patients and identified IL-7R as a potential early diagnostic biomarker for PDAC. Furthermore, we found that IL-7R had improved diagnostic performance when combined with CA19-9. Our previous study's results with 23 individuals were validated in a cohort of 522 patients. Our findings suggested that IL-7R in combination with CA19-9 could have important clinical implications that contribute to an earlier PDAC diagnosis and improved patient survival. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer for which no early diagnostic method is available. The immune surveillance hypothesis suggests that the immune system plays crucial roles in tumor development and progression. We validated a PDAC-specific biomarker derived from peripheral blood mononuclear cells (PBMCs) to facilitate early PDAC diagnosis. mRNA levels of interleukin-7R (IL-7R), reportedly a potential immunological marker for PDAC, were measured in PBMCs isolated prospectively from healthy controls (n = 100) and patients with PDAC (n = 135), pancreatic cysts (n = 82), chronic pancreatitis (n = 42), acute pancreatitis (n = 47), and other malignancies (n = 116). The IL-7R level was significantly higher in patients with PDAC than in healthy controls, patients with benign pancreatic disease, and patients with other malignancies. As diagnostic parameters, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IL-7R were 58.5%, 92%, 90.8%, 62.2%, and 72.8%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.766. IL-7R levels did not differ between resectable and unresectable PDAC cases. The combined measurement of IL-7R and carbohydrate antigen 19-9 (CA19-9) significantly improved the diagnostic parameters and AUROC compared with the use of IL-7R or CA19-9 alone. IL-7R is significantly upregulated in PBMCs in patients with PDAC, and it may be a novel diagnostic marker for PDAC. The combined use of IL-7R and CA19-9 enhanced the diagnostic performance.