| Objectives:Gallbladder cancer (GBC) is a highy malignant, highly aggressive and highly lethal tumor of the digestive tract. Due to the hidden occurrence of this cancer and no specific clinical manifestations, it's difficulty to early diagnosis and no effective treatment programs and so on. A definite diagnosis in the majority of the patients is often late, precluding curative surgical resections. The pathogenesis of gallbladder cancer is not clear, and there is an urgent need to explore the relevant pathological mechanisms and effective diagnosis and treatment strategies. The aim of this study is to find a candidate oncogene from the different expressed genes in gallbladder cancer and the adjacent normal tissue, and to determine its clinical significance in the correlation between the multistage pathogenesis and the clinicopathologic parameters of gallbladder cancer. Thereafter to provide new research clues for the diagnosis and treatment for gallbladder cancer patients.Methods:We used Agilent mRNA expression profiling technique to analyze the differential expression genes of gallbladder cancer and matched normal tissues.The target gene was selected by molecular function associated pathway analysis.Then the differetially expression of this gene in chronic cholecystitis, precancerous lesions and gallbladder cancer multistage was confirmed by immunohistochemical techenique, and we analyzed its correlation with the clinicopathological parameters of gallbladder cancer use the SPSS 19.0 software.Results:1. We use mRNA chip detection of differentially expressed genes in gallbladder cancer and paracancerous tissue and showed that 379 genes was up-regulated include OLFM4. A total of 631 differentially expressed genes were screened by Agilent mRNA chip(SurePrint G3 Human Gene Expression 8x60K v2 Microarray) in 5 gallbladder cancer and matched normal tissues. Among them, 379 genes were up-regulated, such as OLFM4, CDH3 and STYXL1, and there were down-regulated genes, such as YKT6, LUZP1, FBLN1;2. The expression location of OLFM4 gene in the clinical tissue samples of gallbladder was transferred from the nucleus to the extracellular with the development of the multistage carcinogenesis, and the expression of the OLFM4 gene was gradually increased in this stage.2.1 OLFM4 expression location: OLFM4 expression location in the multi-stage development of gallbladder cancer transferred from the nucleus to the extracellular .OLFM4 was mainly expressed in the nucleus in chronic cholecystitis tissues, in several cases, was found expressed in the cytoplasm; in precancerous lesions, it mainly expressed in cytoplasm and extracellular domain; and in gallbladder cancer, it mainly expressed in the extracellular domain;2.2 The relationship between the OLFM4 expression rate and multistage carcibogenesis: OLFM4 expression rate in chronic cholecystitis, precancerous lesions and gallbladder cancer successively increased. The expression level of OLFM4 in gallbladder cancer was higher than that in chronic cholecystitis (p<0.0167). The expression level of OLFM4 in gallbladder precancerous tissue was higher than that in chronic cholecystitis (p <0.0167). The expression level of OLFM4 in gallbladder cancer was higher than that in precancerous lesion, but the difference was not statistically significant (p = 0.192> 0.0167).2.3 OLFM4 expression intensity and the relationship between the multistage carcinogenesis: OLFM4 expression in chronic cholecystitis, precancerous lesions and gallbladder cancer successively increased, the expression intensity of OLFM4 in gallbladder cancer tissue is higher than that in chronic cholecystitis, the difference was statistically significant (p <0.0167). The expression intensity of OLFM4 in gallbladder cancer was higher than that in precancerous lesion (p <0.0167). The expression intensity of OLFM4 in gallbladder cancer was higher than that in precancerous lesion, but the difference was not statistically significant (p = 0.123>0.0167);2.4 OLFM4 expression and the relationship between other clinopathological parameters was no significant: In the subgroup of gallbladder cancer, OLFM4 expression were not significantly correlated (p > 0.05) with gender, age, T stage, N stage, clinical stage, and degree of differentiation.Conclusions:1. OLFM4 may play a different roles in the development of gallbladder multistage carcinogenesis, with stage-specificity;2. OLFM4 may be involved in the promotion of chronic cholecystitis - precancerous lesions - gallbladder cancer development process. |
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