Abstract:

Objective

To investigate the expression of human epidermal growth factor receptor 2 （Her2） and Split hairy enhancer 1 （Hes1） among chronic superficial gastritis （CSG）-intestinal metaplasia （IM）-intestinal type gastric cancer （IGC） in Correa cascade， exploring the molecular mechanism of IGC pathogenesis.

Methods

Immunohistochemistry （IHC） was used to detect the expression levels of Her2 and Hes1 proteins in 30 CSG， 41 IM， and 135 IGC specimens.Western blot was used to detect the expression levels of these two proteins in the gastric epithelial cells GES-1， human IGC cell lines NCl-N87， and MKN74. The spatial location information of Her2 and Hes1 proteins in CSG gastric gland was observed， their different expressions in the gastric pit，isthmus， neck， basal regions， IM， IGC， and different cell lines were compared One-way analysis of variance was used for comparison of means among multiple groups， and LSD t test was used for post hoc pairwise comparisons. Mann-Whitney U test was used to compare the medians of two groups， and Kruskal-Wallis （KW） H test was used to compare the medians of multiple groups with Bonferroni correction. Spearman rank analysis was used for correlation statistics.

Results

IHC results showed that the expression of Her2 （+++） in the isthmus， neck， basal region， IM and IGC was lower than that in the pit [1（3.3 %），0（0.0 %），0（0.0 %），4（9.8 %），10（7.4 %） vs 14（46.7 %）；all P ＜ 0.05］.The expressions of Her2 in the isthmus and IM was moderate， both higher than that in the neck， base，and IGC （P ＜ 0.001）. The expression of Her2 was the weakest in the neck， base， and IGC， and there was no significant difference among them （P ＞ 0.05）. The expression of Hes1 （++） in the isthmus，neck， basal region， IM and IGC was higher than that in the pit [9（30.0 %），4（13.3 %），21（51.2 %），39（28.9 %）比0（0.0 %）； all P ＜ 0.05］. The expression of Hes1 is strongest in the basal region，higher than that in the isthmus， neck， IM and IGC （P ＜ 0.001）. The expression of Hes1 in IM and IGC was stronger than that in the isthmus and neck， respectively （P ＜ 0.05）. There was no significant difference of the expression of Hes1 between IM and IGC， and between isthmus and neck （P ＞ 0.05）.The expression of Her2/Hes1 was significantly negatively correlated in the pit， isthmus， neck， basal region， IM， and IGC （r_s = - 0.794， r_s = - 0.300， r_s = - 0.834，r_s = - 0.921， r_s = - 0.258， r_s = - 0.528，all P ＜ 0.05）. Western blot results revealed that the expression of Her2/Hes1 was significantly negatively correlated in GES-1， NCl-N87 and MKN74 （r_s = - 0.776， r_s = - 0.671， r_s = - 0.614， all P ＜ 0.05）.

Conclusions

In the Correa cascade from CSG to IM， eventually progressing to IGC，Her2 and Hes1 proteins exhibited a negative correlation. Compared with the pit， Her2 expression was gradually decreased with the progression of the disease， while Hes1 expression was moderately upregulated.

Key words: Her2, Hes1, Correa cascade, Intestinal-type gastric cancer, Negative correlation