Ivan Kruljac1, Ivan Vurnek2, Sebastian Maasberg3, Davor Kust4, Kristina Blaslov5, Blaženka Ladika Davidović4, Mario Štefanović6, Alma Demirović7, Alen Bišćanin8, Jakša Filipović-Čugura9, Jasmina Marić Brozić4, Ulrich-Frank Pape3, Milan Vrkljan5. 1. Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. ivkruljac@gmail.com. 2. University of Zagreb School of Medicine, Zagreb, Croatia. 3. Department of Hepatology and Gastroenterology, ENETS Center of Excellence for Neuroendocrine Tumors, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany. 4. Department of Oncology and Nuclear Medicine, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia. 5. Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. 6. Clinical Institute of Chemistry, University Hospital Center "Sestre Milosrdnice", University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. 7. Department of Pathology, University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. 8. Department of Gastroenterology and Hepatology, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia. 9. Department of Surgery, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia.
Abstract
BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.
BACKGROUND:Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS:CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS:CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.
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