| [Background]Analyzed so far, Since its initial identification and cloning in 2002, MTDH(Metadherin)has emerged as an important oncogene that is overexpressed in several carcinomas. It plays a significant role in the progression of tumors, and be involved in invasion, metastasis, angiogenesis, chemoresistance and prognosis. However, relatively little knowledge is available related to the role of MTDH in gastric carcinoma between the expression pattern and clinicopathological features. And little is known about the role of SNPs of MTDH gene in gastric carcinoma.[Purposes]Our study is to examine the pattern of MTDH gene expression and its relationship with clinicopathological featμres in gastric carcinoma, and to evaluate the role of SNPs of MTDH gene in tumorigenesis and progression of gastric carcinoma.[Methods]Specimens from 168 patients with aggressive gastric carcinoma were investigated by immunohistochemistry for MTDH expression. Varioμs clinicopathological factors including survival status were studied by statistical analysis. 5 SNPs variants of MTDH, which obtained from 428 gastric carcinoma cases and 200 healthy controls, were detected by LDR-PCR gene sequencing to determine the genotypes and allele frequencies.[Results]1. MTDH were expressed on nuclear membrane, which significantly lowly expressed in most normal tissues of distant margin, compared with intestinal metaplasised tissue.2. MTDH were significantly overexpressed in gastric carcinoma patients (P<0.001). In different areas of the tumors, its expression was rised at the first, then declined However, the differences were not significant(P=0.244). MTDH expression was correlated with the age of patient (R=0.152, P=0.048).3. Additionally, neither in the different areas of the tumors nor lymph nodes metastasis tissues, MTDH expression was demonstrated no significant difference (P=0.244 and P=0.718).4. MTDH expression levels were correlated with survival time in intra-mucosal, invasive front and lymph nodes(R=-0.134/R=-0.179/R=-0.233). Those patients with overexpressed MTDH in invasive front or lymph nodes had shorter survival time (P=0.021and P=0.005). Besides, the age and the MTDH expression level in lymph nodes were independent prognostic factors by multivariate analysis.5. SNPs detection ilustrated that genotype and allele frequency of rs2512450, but rs2438215, rs2449512, rs7754 and rs2513973, were significantly different between gastric carcinoma patients and the controls (p<0.05). There was a significantly incresed gastric cancer risk (OR. 1.890) with G allele.6. Relations between the differences of the genotypes of rs2512450 and clinicopathological parameters of gastric cancer patients were found in ages≥60, Borrmann classification of ulcerated or infiltrative, lymph node metastasis.7. Overall survivals of the gastric cancer patients were significantly different among different rs2512450 genotypes, bμt rs2438215, rs2449512, rs7754 and rs2513973.[Conclusion]1. MTDH expression level was significantly elevated in intestinal metaplasised and gastric carcinoma tissue, which indicated that MTDH might involved in intestinal metaplasis and maintaining of gastric carcinoma phenotype and invasiveness of cancer cells.2. High MTDH expression in invasive front or lymph nodes correlates with poor overall survival in gastric carcinoma patients.3. The age and the MTDH expression level in lymph nodes were independent prognostic factors, indicating that MTDH may be a potential prognostic factor in gastric carcinoma.4. MTDH rs2512450 polymorphism may be associated with the risk of developing gastric carcinoma in Chinese southren population, and influences ages of patients, Borrmann classification and metastatic ability of gastric carcinoma.5. Overall survivals of the gastric cancer patients were significantly different among different rs2512450 genotypes, but rs2438215, rs2449512, rs7754 and rs2513973.6. It should not be deemed that rs2512450, rs2438215, rs2449512, rs7754 and rs2513973 SNPs of MTDH affect prognosis of gastric carcinoma. |
PDF Full Text Request