Abstract:

Background and purpose: In the process of gastric cancer development, cytothesis and apoptosis, and endoplasmic reticulum stress (ERS) are very important pathological processes. Glucose regulated protein 78 (GRP78) and phosphorylated form of extracellular signal-regulated protein kinase (pERK) play important roles in it. This study aimed to investigate the expression of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis, and the role of GRP78 and pERK in the development of gastric adenocarcinoma. Methods: Gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis tissues in 60 cases respectively were employed in the study. We chose 25 fresh tissue samples from each group, and the level of GRP78 and pERK mRNA in different tissues were detected by RT-PCR assay. The expressions of GRP78 and pERK in different paraffin samples were detected using immunohistochemistry assay. In addition, the relationships between GRP78 and pERK expression and age, gender, differentiation, invasion, disease stage, and lymphoid node metastasis were analyzed. Results: The expression level of GRP78 and pERK mRNA in gastric adenocarcinoma(1.26±0.18, 2.35±0.36) were significantly higher than chronic atrophic gastritis (0.89±0.25, 1.18±0.25) and superficial gastritis (0.29±0.09, 0.68±0.10, P<0.01). The positive ratio of GRP78 expression in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis were 78.3%, 46.6%, 6.7%. The positive ratios of pERK expression were 88.3%, 43.3%, 5.0%, respectively. The GRP78 and pERK expression in different tissues were significantly different (P<0.01). GRP78 and pERK expression were positively correlated with differentiation, disease stage and lymph node metastasis. There was a positive correlation between the gene and protein expression of GRP78 and pERK with a Pearson correlation value of 0.307 and 0.368, respectively. Both univariate and multivariate analysis revealed that GRP78 was related to the prognosis of gastric adenocarcinoma. Conclusion: GRP78 and pERK may play an important role in the transition of normal gastric cells to malignant cells. The expression of these two genes enhances tumor progression. Overexpression of GRP78 and pERK is significantly correlated with poor prognosis in patients with gastric adenocarcinoma. The determination of the expression of GRP78 and pERK might be helpful for the prevention, early diagnosis of gastric carcinoma. Particularly, GRP78 is valuable for the judgement of prognosis, and might be a new target for the treatment of gastric adenocarcinoma.

Key words: GRP78, pERK, Gastric adenocarcinoma