Gastric
adenocarcinoma is one of the most common
cancers in Asian countries including China. Although its incidence rates in the West are lower than that in Asia,
gastric cancer is still a major health problem worldwide, being second only to
lung cancers in the number of deaths it causes. Helicobacter pylori
infection has been identified as the major pathogen, but the detailed pathogenesis of gastric
carcinoma remains elusive. Due to the lack of suitable and specific
biomarkers for early detection, most cases of the disease are diagnosed at late stages and the survival rate is low. In this study, we used a proteomic approach to globally analyze the
protein profiles of paired surgical specimens of primary gastric
adenocarcinoma and nontumor mucosa aiming at identifying specific disease-associated
proteins as potential clinical
biomarkers and for carcinogenetic study. Compared to nontumor tissues, multiple
protein alterations were found in
tumor tissues. Some of these alterations involve variations in the expression of cytoskeleton
proteins, including an increase in
cytokeratin 8 and
tropomyosin isoform and a decrease in
cytokeratin 20. Co-up-regulations of
heat-shock proteins and glycolytic
enzymes were observed in
tumor tissues, indicating self-protective efforts of cells and the growing energy requirement during malignant transformation. Diverse regulations also occurred with
proteins involved in cell proliferation and differentiation, such as
GMP reductase 2 and
creatine kinase B, and
proteins bearing potential
tumor suppressor activities, including
prohibitin and
selenium binding protein 1. More interestingly, a human stomach-specific
protein, 18 kDa antrum mucosa
protein, was found to be dramatically under-expressed in
cancer tissues, implicating a possible special pathological role for this
protein in gastric
carcinogenesis. Further comprehensive evaluation by globally considering the altered factors may result in the discovery of a
biomarker index for effective assessment of the disease and may provide in-depth information for better understanding the pathogenesis of
gastric cancer.