Utility of chromogranin B compared with chromogranin A as a biomarker in Japanese patients with pancreatic neuroendocrine tumors

Abstract

Objective: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. Methods: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features. Results: The diagnostic ability of chromogranin B was as good as chromogranin A. The area under the curve was 0.79 for chromogranin B (sensitivity/specificity: 72%/77%), and 0.78 for chromogranin A (sensitivity/specificity: 79%/64%). Chromogranin B was not affected by proton pump inhibitor use and age, which affected chromogranin A. The number of cases without liver metastases was larger in pancreatic neuroendocrine tumor patients with positive chromogranin B and negative chromogranin A. Though chromogranin A significantly elevated cases with proton pump inhibitor treatment and had positive correlation with age, chromogranin B did not have the tendencies. However, both chromogranin B and chromogranin A elevated in the case with renal impairment. In addition, the logistic regression analysis showed that chromogranin B was superior to chromogranin A in differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases. Conclusions: Compared with chromogranin A, chromogranin B may be more useful during proton pump inhibitor treatment and can detect tumors without liver metastases. In addition,

Lower serum chromogranin B level is associated with type 1 diabetes and with type 2 diabetes patients with intensive conservative insulin treatment

“…Serum CgA and CgB have higher levels in blood and correlate with each other in neuroendocrine tumors of various locations including foregut, midgut and adrenal medulla [2][3][4]. Interestingly, CgA and CgB levels did not correlate with each other and changed in different directions in type 1 diabetes mellitus.…”

“…From the total of 94 control subjects, 62 and 47 age and sex matched subjects were selected via propensity score matching technique as the control population for type 1 and type 2 diabetes patients, respectively. Analysis on CgA was performed only on data where no CgA influencing factor was present [3,4,7]. Laboratory and anamnestic data of study subjects are summarized in Tables 1 and 2. Serum CgA level was significantly higher (p = 0.0348) in type 1 diabetes patients than that of healthy controls (Table 1), in accordance with our previous reports [8].…”

“…a Excluding the measurement of study subjects, who had any condition leading to chromogranin A elevation [ 3 , 4 , 7 ]. Remaining number of observations was 91 and 56, respectively…”

“… Values are expressed as mean ± standard deviation, unit of anamnestic data is the number of observations eGFR Estimated glomerular filtration rate, HbA 1C Glycated hemoglobin a Excluding the measurement of study subjects, who had any condition leading to chromogranin A elevation [ 3 , 4 , 7 ]. Remaining number of observations was 64 and 43, respectively …”

“…Serum CgA is routinely used as a biomarker for neuroendocrine tumors [2]. Serum levels of CgB also rise in pancreatic neuroendocrine tumors, however, it is less commonly used as a diagnostic tool [3]. Measurement of CgB can be advantageous in patients with impaired renal function and/or undergoing antacid therapy, which both may result in false positive CgA concentrations [3,4].…”