Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

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

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.

Vitamin D status in South Korean population: Seven-year trend from the KNHANES.

Vitamin D deficiency has become one of the most prevalent health problems in modern society. However, there has been no study that has reported the trend of vitamin D status in Asia. We performed an observational study to investigate the trend of vitamin D status in South Korea based on a representative national database acquired from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2014. A total of 39,759 patients were included in the final analyses. Serum 25-hydroxyvitamin D (25 (OH)D) levels were measured by radioimmunoassay. The overall mean serum level of 25 (OH)D was 45.7 nmol/L in males and 40.9 nmol/L in females in KNHANES 2008 to 2014. There was a significant trend toward lower serum 25 (OH)D levels from 2008 to 2014 in males by -1.2 (95% confidence interval [CI] -1.5 to -0.9) nmol/L per year and in female by -0.7 (95% CI -0.9 to -0.4) nmol/L per year. The overall mean serum level of 25 (OH)D in 2008 was 53.0 nmol/L in males and 45.7 nmol/L in females. It decreased to 43.2 nmol/L in males and 39.2 nmol/L in females in 2014. Vitamin D deficiency, defined as the serum 25 (OH)D level of <50 nmol/L, was found in 65.7% of males and 76.7% of females in overall population. A significant increasing trend of vitamin D deficiency was also observed. The prevalence of vitamin D deficiency in 2008 was 51.8% in males and 68.2% in females, but rose to 75.2% and 82.5%, respectively, in 2014. The present study demonstrated that vitamin D status in South Koreans is still deteriorating. More extensive and proactive measures are needed to improve vitamin D status in South Korea.