Calprotectin and Calgranulin C as Biomarkers of Pancreatic Tumors: Baseline Levels and Level Changes after Surgery.

Michal Holub,Alžběta Stráníková,Eva Bartáková,Jan Máca,Simona Arientová,Miroslav Ryska,Marie Blahutová,Eva Koblihová

doi:10.1155/2019/6985703

Abstract

Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.

Highlights

Calprotectin, known as S100A8/9, and calgranulin C, known as S100A12, are calcium-binding proteins stored in epithelial cells and phagocytes
The baseline serum levels of calprotectin and calgranulin C were evaluated in an initial cohort of 98 patients who either had benign pancreatic tumors or histologically confirmed malignant pancreatic tumors, including ductal adenocarcinoma, neuroendocrine tumors, and mucinous cystadenocarcinoma; 15 patients with biliary carcinoma, inconclusive histology findings, intraductal papillary mucinous neoplasia, or another type of tumor were excluded from the evaluation
The patients with malignant tumors were significantly older than the healthy controls and the patients with benign tumors, and no differences were observed between the cohorts with malignant and benign tumors with regard to their baseline serum C-reactive protein (CRP) levels, white blood cell (WBC) counts, and reference values

Summary

Introduction

Calprotectin, known as S100A8/9, and calgranulin C, known as S100A12, are calcium-binding proteins stored in epithelial cells and phagocytes. The intracellular roles of calprotectin and calgranulin C are associated with calcium regulation and cell motility When these proteins are released extracellularly, they perform many actions, including stimulating neutrophil adhesion, migration, and release from the bone marrow and cytokine production by monocytes and epithelial cells. Calprotectin and calgranulin C have antibacterial and antiparasitic activities and have been shown to play roles in skin wound healing and liver and musculoskeletal regeneration [1]. Both proteins stimulate proinflammatory activities and reactions to Mediators of Inflammation sterile injuries, as has been demonstrated after severe trauma and major surgery [2, 3]. Calprotectin and calgranulin C have been implicated in many human diseases, such as sepsis, Still’s disease, rheumatoid arthritis, and laryngeal and pancreatic cancer [4,5,6,7,8,9]

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