Identification of differentially expressed proteins in colorectal cancer by proteomics: down-regulation of secretagogin.
To identify proteins with colorectal cancer-specific regulation, comparative 2-DE of individual-matched normal and neoplastic colorectal tissue specimens was performed. We found 15 protein spots with concordantly increased and 20 protein spots with concordantly decreased intensity in tumor tissue (expression regulation more than fivefold). Nine of these proteins were identified by MS/MS. Interestingly, one of the proteins, which exhibited a marked down-regulation in colorectal cancer tissues, was the recently identified endocrine cell-expressed protein secretagogin. The reduction of the secretagogin content in colorectal cancer tissues was confirmed by comparative immunoblotting (n = 17) and RT-PCR (n = 22) as well as by immunohistochemistry (n = 45) of individual-matched neoplastic and normal colorectal tissue specimens. Immunohistochemistry revealed absence of secretagogin-expressing cells in most of the colorectal cancer tissue specimens. However, some colorectal cancers were characterized by secretagogin-expressing cells. In normal mucosa, positively stained cells exhibited a neuroendocrine cell-characteristic morphology and mucosal location. In colorectal cancer tissues, secretagogin-expressing cells were characterized by a malignant morphology. Our findings might represent the basis for the clinical application of secretagogin as a biomarker for a distinct subgroup of colorectal cancers.
Xing
Xiaoming
X
Department of Pathology and Pathophysiology, Center for Environmental Genomics, School of Medicine, Zhejiang University, Hangzhou, China.
Lai
Maode
M
Gartner
Wolfgang
W
Xu
Enping
E
Huang
Qiong
Q
Li
Han
H
Chen
Guangdi
G
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064046:Secretagogins
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D020543:Proteome; D012333:RNA, Messenger; C576556:SCGN protein, human; D064046:Secretagogins