Proteomic identification of differentially-expressed genes in human gastric carcinomas.
Although genetic alterations in proto-oncogenes, tumor-suppressor genes, cell cycle regulators, and cell growth factors have been implicated in the process of human gastric carcinogenesis, the principle carcinogenic mechanisms are not fully understood. In this study, we used a proteomic approach to search for genes that may be involved in gastric carcinogenesis and that might serve as diagnostic markers. We identified nine proteins with increased expression and 13 proteins with decreased expression in gastric carcinomas. The two most notable groups included proteins involved in mitotic checkpoint (MAD1L1 and EB1) and mitochondrial functions (CLPP, COX5A, and ECH1). This suggested that there are links between dysfunctions in these processes and gastric carcinogenesis. We also observed the differential expression of HSP27 and CYR61 proteins in gastric carcinoma, whose expression is known to be altered in other types of tumors. Furthermore, the study identified proteins whose function in gastric carcinomas was previously unsuspected and that may serve as new molecular markers for gastric carcinomas. Importantly, immunohistochemical analyses confirmed that the levels of expression of MAD1L1, HSP27, and CYR61 were altered in gastric carcinoma tissues. Therefore, our study suggested not only that the proteins identified in this study can be useful diagnostic markers but also that a proteomics-based approach is useful for developing a more complete picture of the pathogenesis and function of gastric carcinomas.
Nishigaki
Ryuichi
R
Department of Human Genome Science (Kirin Brewery), Graduate School of Medical Science, Tottori University, Nishi-cho 86, Yonago, Tottori 683-8503, Japan.
Osaki
Mitsuhiko
M
Hiratsuka
Masaharu
M
Toda
Tosifusa
T
Murakami
Kaori
K
Jeang
Kuan-Teh
KT
Ito
Hisao
H
Inoue
Toshiaki
T
Oshimura
Mitsuo
M
D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008928:Mitochondria / Q000378:metabolism; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics / Q000379:methods*; D013274:Stomach Neoplasms / Q000378:metabolism*; D015854:Up-Regulation