Abstract
Simple SummaryDespite 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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality worldwide and accounts for 6% of annual cancer deaths
We collected peripheral blood samples from patients diagnosed with PDAC, benign pancreatic cysts, chronic pancreatitis (CP), acute pancreatitis (AP), and other systemic cancers
Quantitative Real Time PCR of IL-7R Gene Expression We reported previously that 364 genes are differentially expressed in the peripheral blood mononuclear cells (PBMCs) of patients with PDAC compared with healthy controls [9]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality worldwide and accounts for 6% of annual cancer deaths. Various treatment strategies for PDAC have been developed, the 5-year survival rate remains 3–5% [1,2,3,4]. Most patients with PDAC are asymptomatic until the disease progresses, and it metastasizes in approximately 50% of cases. 10–20% of patients with PDAC are candidates for surgical resection, which is the only treatment option that offers a potential cure [1,2]. To improve PDAC prognosis and treatment, early detection and surgical resection are crucial. CA19-9 assessment does not enable the discrimination of PDAC from other benign diseases, and false-positive results may be obtained in the presence of host inflammatory responses and obstructive jaundice. CA19-9 analysis generates false-negative results in patients who are Lewis antigen-negative [5]
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