Chromogranin A (CgA) is a useful biomarker for diagnosis and monitoring of the extremely heterogeneous neuroendocrine tumors (NETs) [1]. NETs can arise in the stomach, intestines, rectum, pancreas, lungs, and adrenal and thyroid glands. One common feature of all NETs is that they originate from specialized cells belonging to the neuroendocrine (NE) system [2]. NE cells produce, mature, and exocytose secretory granules containing general neuroendocrine markers, such as CgA, and site-specific markers, such as amine and peptide hormones [3]. Although some NE cells are localized to a certain anatomic site and have precise functions (e.g., adrenal, pituitary, parathyroid), those belonging to the diffuse NE system make up a poorly defined thin layer dispersed throughout the bronchopulmonary and gastrointestinal systems [4]. Because NETs can arise in diverse anatomical sites and exhibit varying degrees of hormone secretion, diagnosis via tissue biopsy or imaging is limited. A specific amine or peptide hormone may serve as a biomarker for a specific type of NET. For example, gastrin may be used as a biomarker for gastrinoma, insulin for insulinoma, serotonin for small bowel NET, and glucagon for glucagonoma [4]. However, a more universal biomarker for all of these conditions is needed to facilitate early diagnosis. To date, CgA is the best available circulating biomarker for such applications.
CgA was the first of the eight members of the granin family to be identified. Granins are the major components of the soluble core of dense-core secretory granules in NE cells and are therefore secreted by these cells. Additionally, granins are thought to play important roles in granulogenesis, secretory protein sorting, and secretory granule maturation and condensation [5, 6]. CgA is a heat-stable, hydrophilic protein composed of 439 amino acids. After translation, CgA undergoes post-translational processing to generate small peptides with specific biological activities, such as pancreastatin (corresponding to residues 250–301) and catestatin (corresponding to residues 352–372) [7]. CgA mRNAs and proteins are found in all types of neurons [8], indicating their potential as universal biomarkers.
Numerous immunoassays have been developed for measuring CgA levels. Among these, the B.R.A.M.S. CgA Ⅱ KRYPTOR assay (ThermoFisher Scientific, Waltham, MA, USA; KRYPTOR) uses time-resolved amplified cryptate emission (TRACE) technology, which allows for spectral and temporal distinction between signals of interest and unwanted background signals [9]. Moreover, the B.R.A.H.M.S. KRYPTOR Compact PLUS analyzer, which is the platform utilized for the assay, is a fully automated random-access system that requires less hands-on time and produces results more quickly.
In this study, we evaluated the analytical performance of KRYPTOR to determine if it may improve workflow in laboratories. Three CgA assays were compared: KRYPTOR, NEOLISA Chromogranin A (EuroDiagnostica, Malmö, Sweden [NEOLISA]), and CgA-RIA CT (CisBio Codolet, France [CgA-RIA]). To assess the analytical performance of KRYPTOR, we evaluated its linearity, precision, and correlation with the other two CgA assays. We also compared measured CgA levels in samples from patients with three different disease entities (NETs, non-NET pancreatic tumors, prostate cancer) to healthy individuals to determine whether serum CgA can be used to discriminate among these groups.