| Backgroud and Objective:The evidence reveales that Wnt signaling pathway not only participates in the regulation of cell proliferation, differentiation, mobilization and apoptosis but also influences and regulates the self-renew and differentia-tion of the stem cells, this pathway is a considerable complex system that involves multiple interacting factors. The abnormal activation of Wnt signaling pathway intimately correlates with the tumorigenesis and progression, because of the regional distinction, a large body of studies more foused on colorectal cancer and mammary cancer than gastric cancer (GC) in occident. However, GC is one of the most common enteron malign-nancies, therefore the relationship between Wnt signaling pathway and the tumorigenesis and progression of gastric cancer has drawn researcher' attention.Wntl gene is one of Wnt gene family, also is the start factor of Wnt signaling pathway.β-catenin is the core of this classics pathway, it plays important effect in the Wnt signaling pathway and in the tumorigenesis and progression.Lgr5, also known as GPR49, is a large protein consisting of 18 extra-cellular leucine-rich repeats together with a seven-transmembrane region, one of the G protein-coupled receptors family; it is the newly target gene of the Wnt signaling pathway and the potential stem cell marker.We checked out the expression of Wntl,β-catenin and Lgr5 in gastric various lesion organizations, which are the three important representative factor of Wnt signaling pathway, to investigate the relationship with gastric tumorigenesis and progression, also to approach the specificity of Lgr5+ cells as the gastric cancer stem cells. Through the study of relationship between Wntl,β-catenin and Lgr5, then froming a complete pathway to investigate the role of Wnt signaling pathway in gastric cancer, to approach the clinicopathological significance and the possible molecular mechanism of Lgr5 in gastric tumorigenesis and progression. It is valuable in the study of pathogenesis mechanism, prophase dignosis, prevention of GC, it also provides the new treatment target of GC.Mathods:1. Collecting the clinical specimens of gastric lesions, then making experimental groups. It contains 11 cases of adjacent normal gastric mucosa, 23 cases of gastric precancerous lesions (including 8 cases of gastric epithelial dysplasia and 15 cases of intestinal metaplasia mucosa),14 cases of early gastric adenocarcinoma and 30 cases of advanced gastric adeno-carcinoma.2. Immunohistochemistry SP method was used to examine for the expression of Wntl,β-catenin and Lgr5 in adjacent normal gastric mucosa, gastric precancerous lesions, early gastric adenocarcinoma and advanced gastric adenocarcinoma.3. Analysis the date use SPSS11.5, significance was set at p<0.05.Results:1. The expression of Wntl in gastric various lesionsIn adjacent normal gastric mucosa, the expression of Wntl was very low or absence, the positive expression rate was 18.2%, in gastric pre-cancerous lesions, early and advanced gastric cancer, the expression of Wntl is high, the positive expression rates were 87.0%,85.7%,86.7%, datas showed significant difference between adjacent normal gastric mucosa and gastric precancerous lesions, early gastric cancer, advanced gastric cancer (p<0.01). But the expression of Wntl between gastric precancerous lesions and early gastric cancer, advanced gastric cancer, there was not significant difference (p>0.05).2. The expression ofβ-catenin in gastric various lesionsIn adjacent normal gastric mucosa, the expression ofβ-catenin was mainly located in cell membrane, in gastric precancerous lesions, early and advanced gastric cancer, the expression of membrane was decreased, the absence of the expression of membrane was increased and the expression of β-catenin locating in cytoplasm/nucleus was also increased.β-catenin' abnormal expression (locating in cytoplasm/nucleus and the absence of membrane) rates in adjacent normal gastric mucosa, gastric precancerous lesions, early gastric cancer and advanced gastric cancer were 9.1%,82.6%, 100.0%,96.7%, there was significant difference between them (p<0.01). But the abnormal expression ofβ-catenin between gastric precancerous lesions, early gastric cancer and advanced gastric cancer, there was not significant difference (p>0.05).3. The expression of Lgr5 in gastric various lesionsIn adjacent normal gastric mucosa, the expression of Lgr5 was very low in the base and the isthmus of the gastric gland, the expression of Lgr5 was absent in the epithelial of gastric mucosa. The positive expression rates of Lgr5 in adjacent normal gastric mucosa, gastric precancerous lesions, early gastric cancer and advanced gastric cancer were 18.2%,78.3%,78.6%, 80.0%, there was a significant difference between them (p<0.01). But the expression of Lgr5 between gastric precancerous lesions, early gastric cancer and advanced gastric cancer, there was not significant difference (p >0.05).4. The relation of Wntl,β-catenin and Lgr5 in gastric cancerThe expression between Wntl and Lgr5 had a significant consistency (p<0.05) and the relationship between them was positive (r=0.414); between the expression ofβ-catenin and the expression of Wntl, Lgr5, there was not relationship (p>0.05).5. The relationship between the expression of Wntl,β-catenin, Lgr5 and clinical pathological featuresNo significant relationship was found between the expression of Wntl,β-catenin, Lgr5 and clinical pathological features, such as ages, tumour size, differentiation, et al (p>0.05).Conclusion:1. The expression tendency of Wntl,β-catenin and Lgr5 raised up in adjacent normal gastric mucosa, gastric precancerous lesions, early gastric cancer and advanced gastric cancer, it indicates that Wnt signaling pathway is activated in gastric tumorigenesis and progression, having intimate correlation with gastric tumorigenesis and progression. 2. The expression of Wntl,β-catenin and Lgr5 in gastric precancerous lesions was notablely higher than in adjacent normal gastric mucosa, but no difference between gastric precancerous lesions and early gastric cancer, advanced gastric cancer, it indicates that the activation of Wnt signaling pathway is the early event in gastric lesions.3. The expression between Wntl and Lgr5 had a significant consistency, perhaps Lgr5 is the target gene of Wnt signaling. No correlation between Wnt1 andβ-catenin, maybe there are other Wnt proteins participating in the regulation of Wnt signaling pathway.4. The expression of Lgr5 in gastric various lesions indicates that Lgr5 intimately correlates with gastric tumorigenesis and progression.
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