Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was identified in islet β cells by Wagner. SCGN is a six EF-hand Ca2+-binding protein, primarily expressed on the neuroendocrine axis and the central nervous system. The protein has abundant biological functions. A certain concentration of calcium ion can lead to conformation change of SCGN, resulting in the change of intracellular signal transduction. Preliminary studies showed that SCGN would be used to treat stress reaction, such as mental illness (depression), burns or post-traumatic stress disorder and chronic stress reaction caused by pain. In Alzheimer's disease, the expression of SCGN in the hippocampus can boycott neurodegeneration. In neuroendocrine tumors, SCGN presents a good consistency with neuroendocrine markers such as CgA, Syn, and NSE, with a higher overall sensitivity and specificity. In addition, SCGN is released into serum after neural damage in cerebral ischemic diseases, suggesting that SCGN can be used as a marker for brain trauma. In this article, we review the recent research progress of secretagogin, focus on its distribution and functions in various tumorous diseases and non-tumorous diseases, such as Alzheimer's disease.
Alzheimer Disease ; diagnosis ; Biomarkers ; analysis ; Brain Ischemia ; diagnosis ; Calcium ; metabolism ; Hippocampus ; metabolism ; Humans ; Neuroendocrine Tumors ; diagnosis ; Secretagogins ; physiology ; Signal Transduction

Alzheimer Disease ; metabolism ; Animals ; Brain ; metabolism ; Calcium-Binding Proteins ; biosynthesis ; chemistry ; genetics ; Gastrointestinal Tract ; metabolism ; Humans ; Islets of Langerhans ; metabolism ; Neoplasms ; metabolism ; RNA, Messenger ; metabolism ; Secretagogins ; Thyroid Gland ; metabolism

OBJECTIVETo investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.

METHODSClinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.

RESULTSThe expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.

CONCLUSIONNeuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

Adenocarcinoma ; diagnosis ; pathology ; Biomarkers, Tumor ; metabolism ; Chromogranin A ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Secretagogins ; metabolism ; Stomach Neoplasms ; diagnosis ; pathology ; Synaptophysin ; metabolism

Adenoma ; metabolism ; Adrenal Cortex Neoplasms ; metabolism ; Biomarkers, Tumor ; metabolism ; Calcium-Binding Proteins ; metabolism ; Carcinoma, Neuroendocrine ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Neuroendocrine Cells ; metabolism ; Neuroendocrine Tumors ; metabolism ; Secretagogins ; Small Cell Lung Carcinoma ; metabolism

OBJECTIVETo identify the differentially expressed proteins or peptides and potential biomarkers of tumorigenesis for colorectal cancers.

METHODSImmobilized pH gradient two-dimensional gel electrophoresis (2-DE) was used to separate and obtain the differentially expressed protein spots between colorectal cancers and matched normal mucosa. Liquid chromatography/mass spectrometry (LC-MS/MS) was used to characterize these proteins. Selected candidate proteins were further studied by Western blot, semi-quantitative RT-PCR and immunohistochemical staining.

RESULTSThirty-five protein spots showed marked expression changes (more than 5-fold) in colorectal carcinoma compared to normal mucosa. Fifteen proteins were up regulated and 20 were down regulated. Fourteen of these proteins were identified by tandem mass spectrometry, among which secretagogin (SCGN) was down-regulated and glucose-related protein (GRP) 78 was up-regulated in the tumors. The SCGN down-regulation was further supported by Western blot and RT-PCR analyses. Immunohistochemistry revealed that SCGN was strongly expressed in neuroendocrine cells of the colonic crypts and 53 of 54 (98%) neuroendocrine tumors. At protein level, although GRP78 was up regulated in colorectal carcinoma, there was no difference in the mRNA expression level between the tumor and paired normal mucosa.

CONCLUSIONSThe 2-DE combined with MS is a powerful tool for screening potential tumor biomarkers. The differentially expressed candidate proteins identified by 2-DE may be of significance in understanding the tumorigenesis of the colon cancer. SCGN is a potential biomarker for neuroendocrinal differentiation. GRP78 up-regulation in colorectal carcinomas may be related to its post-translational modification.

Biomarkers, Tumor ; genetics ; metabolism ; Calcium-Binding Proteins ; genetics ; metabolism ; Colorectal Neoplasms ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Profiling ; methods ; Gene Expression Regulation, Neoplastic ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Molecular Chaperones ; genetics ; metabolism ; Neuroendocrine Cells ; metabolism ; Neuroendocrine Tumors ; metabolism ; Proteomics ; methods ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Secretagogins