Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis.

OBJECTIVE: Infectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitis METHODS: This study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed. RESULTS: We observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%). CONCLUSION: This study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.

Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis.

BACKGROUND: Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. METHODS AND RESULTS: In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients. CONCLUSION: These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.