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      Combined test of serum CgA and NSE improved the power of prognosis prediction of NF-pNETs

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          Abstract

          Purpose

          Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).

          Patients and Methods

          In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05.

          Results

          Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L ( P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration ( P < 0.001); changes in CgA and NSE concentrations also reflect treatment response ( P < 0.001).

          Conclusion

          CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.

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          Most cited references14

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          ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

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            Chromogranin A--biological function and clinical utility in neuro endocrine tumor disease.

            Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they synthesize, store, and secrete peptides, e.g., chromogranin A (CgA) and amines. A critical issue is late diagnosis due to failure to identify symptoms or to establish the biochemical diagnosis. We review here the utility of CgA measurement in NETs and describe its biological role and the clinical value of its measurement. Literature review and analysis of the utility of plasma/serum CgA measurements in NETs and other diseases. CgA is a member of the chromogranin family; its transcription and peptide processing are well characterized, but its precise function remains unknown. Levels are detectable in the circulation but vary substantially (approximately 25%) depending on which assay is used. Serum and plasma measurements are concordant. CgA is elevated in approximately 90% of gut NETs and correlates with tumor burden and recurrence. Highest values are noted in ileal NETs and gastrointestinal NETs associated with multiple endocrine neoplasia type 1. Both functioning and nonfunctioning pancreatic NETs have elevated values. CgA is more frequently elevated in well-differentiated tumors compared to poorly differentiated NETs. Effective treatment is often associated with decrease in CgA levels. Proton pump inhibitors falsely increase CgA, but levels normalize with therapy cessation. CgA is currently the best available biomarker for the diagnosis of NETs. It is critical to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy. Measurement of plasma CgA is mandatory for the effective diagnosis and management of NET disease.
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              Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis.

              We present evidence that regulation of dense-core secretory granule biogenesis and hormone secretion in endocrine cells is dependent on chromogranin A (CGA). Downregulation of CGA expression in a neuroendocrine cell line, PC12, by antisense RNAs led to profound loss of dense-core secretory granules, impairment of regulated secretion of a transfected prohormone, and reduction of secretory granule proteins. Transfection of bovine CGA into a CGA-deficient PC12 clone rescued the regulated secretory phenotype. Stable transfection of CGA into a CGA-deficient pituitary cell line, 6T3, lacking a regulated secretory pathway, restored regulated secretion. Overexpression of CGA induced dense-core granules, immunoreactive for CGA, in nonendocrine fibroblast CV-1 cells. We conclude that CGA is an "on/off" switch that alone is sufficient to drive dense-core secretory granule biogenesis and hormone sequestration in endocrine cells.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                January 2018
                30 November 2017
                : 7
                : 1
                : 169-178
                Affiliations
                [1 ]Department of General Surgery Zhongshan Hospital, Fudan University, Shanghai, China
                [2 ]Department of Clinical Laboratory Zhongshan Hospital, Fudan University, Shanghai, China
                [3 ]Department of Pathology Zhongshan Hospital, Fudan University, Shanghai, China
                Author notes
                Correspondence should be addressed to W Lou or X Xu: lou.wenhui@ 123456zs-hospital.sh.cn or xuefengxu87@ 123456aliyun.com

                *(Y Lv and X Han contributed equally to this work)

                Article
                EC170276
                10.1530/EC-17-0276
                5776672
                29191920
                c07dc558-3d18-4e69-8d9a-2097c1dd692e
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 09 November 2017
                : 30 November 2017
                Categories
                Research

                chromogranin a,neuron-specific enolase,nonfunctioning pancreatic neuroendocrine tumors,prognosis prediction

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