Research On Mechanism Of NF-κB P65 In The Process Of CagAH· Pylori Infection Leading To Gastric Carcinoma

Background and aims: Gastric adenocarcinoma is the second frequent cancer in the world. Since the 80's of the 20th century, H · Pylori, especially CagA H · Pylori, have received much more attention, because of close association between H · Pylori infection and gastric carcinoma. In 1994, according to the epidemiological studies and regular patterns of occurrence and development of gastric carcinoma, the International Agence for Research on Cancer, belonging to world health organizer, identify H · Pylori as grade â…  carcinogenesis.Nuclear factor of κ B is a sequence-specific transcription factor and exists in the cells of mammal animal. NF- κ B and target genes which regulate the transcription of chemokine and cytokine have been most intensely studied for their involvement in immunity disorder and inflammatory disease. Recently, this transcription factor have been found to regulate the expression of cell proliferation and antiapoptosis genes, which strongly link with neoplasm. NF- κ B has also been shown to be expression and activation in various haematological malignances as well as epithelial tumors such as breast cancer, gastric carcinoma. It is well documented that CagA of CagAH ·Pylori can activate the NF-κ B of gastric epithelial cell and consequently transcribe the genes coding for regulators of cytokines and chemokine leading to gastritis. This investigation is to explore the mechanism of CagAH · Pylori infection leading to gastric carcinoma via observing the expression of NF- κ B p65 mRNA and target genes C-myc, CyclinD₁ , Bcl-xl in the tissues of gastric carcinoma and premalignants.Methods: (1) In the tissue of 290 cases, Rapid Urease Test, Warthin-Starry staining and immunohistochemical staining of CagA protein were used to detect the CagA⁺H · Pylori and CagA^-H · Pylori.(2) The different types of intestinal metaplasia were analysed by HID-AB(pH2.5)-PAS mucin staining and histopathologic observation.(3) The different grades of dysplasia and different types of gastric carcinoma were detected by H · E staining and histopathologic observation.(4) In situ hybrization and Immunohistochemical staining were used to detect the expression of NF- k B p65 mRNA and target genes such as: C-myc * CyclinDi, Bcl-xl in the tissue of chronic atrophy gastritis, intestinal metaplasia, dysplasia and gastric carcinoma.Results: (1) The positive rate of CagA+H ? Pylori infection is highest in the part of gastrical antrum . In the different grades of intestinal metaplasia, dysplasia and different type of gastric carcinoma ,the positive rate of CagA+H ? Pylori is highest in the tissues of intestinal metaplasia type III, dysplasia grade II III and intestinal type gastric carcinoma.(2) Expression of NF- k B p65 mRNA and target genes such as: C-myc* CyclinDi, Bcl-xl is unsignificantly different in the premalignants of H ? Pylori infection(P>0.05).(3) In the tissues of chronic atrophy gastritis, intestinal metaplasia type I — II, intestinal metaplasia type III, dysplasia grade I, dysplasia grade II ■—'III, the expression of NF- k B p65 mRNA is significantly higher in the group with CagA+H ? Pylori than that with CagAH ? Pylori. There is a relationship between CagA+H ? Pylori infection and expression of NF- k B p65 mRNA(P<0.05) in the above mentioned tissues.In the above mentioned tissues, the expression rate of C-myc >. CyclinDi > Bcl-xl genes is higher in the group of CagA+H ? Pylori infection than that of CagA'H ? Pylori infection and there is a significant different in the tissue of intestinal metaplasia type HI, dysplasia grade II —III. The expression of NF- k B p65's target genes has a close relationship with expression of NF- k B p65 mRNA(P<0.05).(4) In the tissue of gastric carcinoma, the expression of NF- k B p65 mRNA and target genes is significantly higher in the group with CagA+H ? Pylori than that of with CagA'H -Pylori. In the clinicalpathologic feature of gastric carcinoma, the expression rates of NF- k B p65 mRNA and it's target gene are significantly higher in intestinal type gastric carcinoma than that of diffuse type gastric carcinoma. High expression of CyclinDi is association with metastasis of lymphoma node and expression of C-myc is link with infiltration of gastric carcinoma.(5) In the lamina propria of chronic atropHy gastritis, intestinal metaplasia, dysplasiaand stroma of gastric carcinoma, the expression of NF- k B p65 mRNA and target genes in the inflammatory cells are observed. Conclusions:(1) Non-cardiac gastric adenocarcinoma of intestinal type is close link with CagA+H ? Pylori infection.(2) CagA+H ? Pylori infection promote the occurrence of intestinal type gastric carcinoma through the expression of NF-k B p65 mRNA> C-myc> CyclinDi, Bcl-xl protein in the tissues of intestinal metaplasia III, dysplasia grade II ^III.(3) There is a different mechanism between the occurrence of intestinal type gastric carcinoma and diffuse type gastric carcinoma, that is, CagA+H ? Pylori infection leads to intestinal type carcinoma by virtue of activation and expression of NF- k B p65 mRNA and it's target genes C-myc, CyclinD^ Bcl-xl in the different lesions of gastric premalignant.(4) NF- k B p65 may be an important link CagA+H ? Pylori infection leading to gastritis, intestinal metaplasia, dysplasia and intestinal type gastric cancer. Inhibiting the NF- k B activation may be prevent the occurrence of intestinal type carcinoma caused by CagA+H ? Pylori infection.