Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways.
The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype.
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.|Poochon Scientific, Frederick, Maryland 21701, USA.
Jian-Jiang
JJ
Hao
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Xiaofei
X
Zhi
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Yeming
Y
Wang
Poochon Scientific, Frederick, Maryland 21701, USA.
Zheng
Z
Zhang
Whiting School of Engineering of Johns Hopkins University, Baltimore, Maryland 21218, USA.
Zeyu
Z
Hao
Poochon Scientific, Frederick, Maryland 21701, USA.
Rong
R
Ye
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Zhijie
Z
Tang
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Fei
F
Qian
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Quhui
Q
Wang
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Jianwei
J
Zhu
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
D002843:Chromatin; D020543:Proteome