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Promoter Methylation and the Expression of RKIP Gene in Gastric Cardiac Adenocarcinoma

Author: LinXinWen
Tutor: DongZhiMing
School: Hebei Medical University
Course: Pathology and Pathophysiology
Keywords: Gastric cardia adenocarcinoma Gene Expression RKIP DNA methylation mRNA
CLC: R735.2
Type: Master's thesis
Year: 2011
Downloads: 44
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Abstract

Objective: cardia adenocarcinoma (gastric cardiac adenocarcinoma, GCA) is gastroesophageal junction cancer type, especially in the northern region of China's common gastrointestinal malignancies. Epidemiological survey found a high incidence of gastric cardia adenocarcinoma incidence and mortality rates have increased year after year. With esophageal cancer in the geographical distribution of clinical symptoms and have similar epidemiological characteristics, and difficult to find early gastric cardia adenocarcinoma, clinical cases, mostly in the late treatment, the treatment less effective, so the pathogenesis of gastric cardia adenocarcinoma and early Diagnosis is particularly important. Currently cardia adenocarcinoma, the molecular mechanism is not very clear, is generally believed that the incidence of adenocarcinoma of the cardia environmental and genetic factors are the result of joint action. To reduce the incidence of gastric cardia adenocarcinoma and mortality study its pathogenesis is necessary. Raf kinase inhibitor protein (Raf kinase inhibitor protein, RKIP) is a mitogen-activated protein kinase (Mitogen-activated protein kniase, MAPK) signal transduction pathway of natural inhibitors, widely present in a variety of organisms involved in intracellular multiple signal transduction pathways regulating effect, its expression decreased with a variety of tumor occurrence, development and metastasis. RKIP abnormal gene expression mechanism for research, in addition to the traditional sense of the genetic causes of disease mechanisms, in recent years, as the representative of a DNA methylation epigenetic changes in tumor pathogenesis research has become a hot topic and received extensive attention . However, RKIP gene promoter methylation lead to aberrant expression of many for gastric cancer, colorectal cancer and other diseases, research on the cardia adenocarcinoma has not been reported at home and abroad. Therefore, in-depth study RKIP gene promoter methylation in the lead role of GCA will be to reveal the pathogenesis of gastric cardia adenocarcinoma provide molecular biological evidence. The study is based on high incidence of esophageal adenocarcinoma of the cardia in Hebei Province as the research object, using methylation-specific PCR (MSP) detect RKIP gene methylation status and cardia adenocarcinoma, invasion and metastasis, combined with immunohistochemistry chemistry and RT-PCR method to detect in the cardia adenocarcinoma and adjacent non-tumor tissue RKIP protein and mRNA expression and expression and the clinical parameters and biological behavior, explore the gene methylation in gastric cardia adenocarcinoma development, invasion, metastasis, thus revealing the molecular level cardia adenocarcinoma mechanisms, such as gene therapy and prognosis provide new theoretical and experimental basis. Method: 1 using the improved methylation-specific polymerase chain reaction (methylation specific PCR, MSP) detected 80 cases of gastric cardia adenocarcinoma and 51 cases of adjacent non-tumor tissues RKIP gene promoter methylation status. 2 using reverse transcription - polymerase chain reaction (reverse transcriptase PCR, RT-PCR) to detect 28 cases of gastric cardia adenocarcinoma, and 24 cases of adjacent non-tumor tissue mRNA expression levels of RKIP. 3 Immunohistochemistry (immunohistochemistry, IHC) SP detected 32 cases of gastric cardia adenocarcinoma, 32 cases of adjacent non-tumor tissue protein RKIP gene expression. 4 using statistical software SPSS13.0 was used for statistical analysis. Results: 1 RKIP gene in gastric cardia adenocarcinoma and adjacent non-tumor tissue methylation rates were 65% (52/80) and 33.3% (17/51), the difference was statistically significant, cardia adenocarcinoma methylation was significantly higher than in adjacent non-tumor group (P lt; 0.001); in cardia adenocarcinoma, Ⅲ, Ⅳ stage methylation rate 31/45 (68.9%) than stage Ⅰ, Ⅱ A base rate of 21/35 (60%), moderately differentiated methylation ratio of 35/52 (67.3%) higher than the incidence of poorly differentiated methylation 17/28 (60.7%), but the difference was not statistically significance (P gt; 0.05). RKIP genes with clinical data such as age, gender, lymph node metastasis, tumor differentiation and TNM stage were independent (P gt; 0.05). 2 RKIP in the cardia adenocarcinoma and adjacent non-tumor group protein expression rates were 43.8% (14/32) and 75% (24/32), the difference was statistically significant, the expression of cardia adenocarcinoma was significantly than in adjacent non-tumor group (P lt; 0.05); in cardia adenocarcinoma, Ⅲ, Ⅳ expression rates of patients with stage 12/26 (46.2%) higher than Ⅰ, Ⅱ expression rates of patients with stage 2 / 6 (3.3%), poorly differentiated adenocarcinoma of the protein expression rate of 5/13 (38.5%) than moderately differentiated adenocarcinoma expression rates 9/19 (47.4%), RKIP protein expression with clinical data such as patient age, gender grouping unrelated (P gt; 0.05), and lymph node metastasis, clinical stage, pathological stage also irrelevant (P gt; 0.05). 3 RKIP gene mRNA in gastric cardia adenocarcinoma tissues, adjacent non-tumor tissues relative expression levels were 0.67 ± 0.41 and 3.46 ± 1.76, cardia adenocarcinoma group was significantly lower than in adjacent non-tumor group, the difference was statistically significant (P lt; 0.05). In the cardia adenocarcinoma, RKIP mRNA expression with clinical data such as patient age, gender grouping unrelated (P gt; 0.05), and lymph node metastasis, clinical stage, pathological stage is also irrelevant (P gt; 0.05). 4 RKIP gene promoter methylation and mRNA expression of the relationship between: cardia adenocarcinoma RKIP gene methylation positive its mRNA expression (0.73 ± 0.43) compared with methylation of the gene mRNA expression of negative GCA volume (0.42 ± 0.35), but the difference was not statistically significant (P gt; 0.05). 5 RKIP gene promoter methylation and protein expression between: cardia adenocarcinoma RKIP gene methylation-positive protein expression was 47.06% (8/17), the gene methylation in protein positive negative rate of 57.14% (4/7), gastric cardia adenocarcinoma methylation positive RKIP protein expression compared with methylation-negative RKIP protein expression is low, the difference was not statistically significant (P gt; 0.05). 6 RKIP protein expression and mRNA expression between: cardia adenocarcinoma RKIP gene protein expression of mRNA expression was 0.65 ± 0.47, cardia adenocarcinoma negative for the gene expression of the mRNA expression was 0.65 ± 0.43, the difference was not statistically significant (P gt; 0.05). Conclusions: 1 RKIP gene methylation in gastric cardia adenocarcinoma was significantly higher than in adjacent non-tumor tissue methylation rates, but RKIP gene methylation and clinical data, suggesting the RKIP gene promoter methylation technology may be associated with the occurrence of gastric cardia adenocarcinoma, and has nothing to do with its development. Meanwhile, RKIP cardia adenocarcinoma in protein and mRNA expression was significantly lower than in adjacent non-tumor tissues, suggesting that abnormal expression of RKIP and cardia adenocarcinoma occurrence. 2 RKIP protein relative expression levels in methylation-positive and methylation cardia adenocarcinoma of the cardia adenocarcinoma negative difference was not statistically significant, and the relative expression of RKIP protein has nothing to do with the clinical data, suggesting that methylation RKIP protein expression may not result in abnormal main reason. 3 RKIP gene mRNA expression in methylation-positive and methylation cardia adenocarcinoma of the cardia adenocarcinoma negative difference was not statistically significant, and RKIP gene mRNA expression and clinical data, suggesting the methyl technology may not lead to abnormal mRNA expression RKIP the main reason.

Promoter Methylation and the Expression of RKIP Gene in Gastric Cardiac Adenocarcinoma

Abstract

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