[Differential expression of secretagogin and glucose-related protein 78 in colorectal carcinoma: a proteome study].
OBJECTIVE
To identify the differentially expressed proteins or peptides and potential biomarkers of tumorigenesis for colorectal cancers.


METHODS
Immobilized 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.


RESULTS
Thirty-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.


CONCLUSIONS
The 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.
Xing
Xiao-Ming
XM
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Wang
Ying-Hong
YH
Huang
Qiong
Q
Lü
Bing-Jian
BJ
Lai
Mao-de
MD
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D055099:Neuroendocrine Cells / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064046:Secretagogins
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C576556:SCGN protein, human; D064046:Secretagogins