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Serial Analysis Of Gene Expression In Adenocarcinoma And Normal Mucosa Of Colon

Posted on:2009-10-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:X L ZhangFull Text:PDF
GTID:1114360245453348Subject:Oncology
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Background and Objective:Colorectal cancer is one of the most common malignant tumors in most regions of the world. Research on molecular level will play an important role in the improvement of tumor diagnosis and treatment. After the finish of human genome project, the research aim at tumor has entered the post-genomic era. The construction of gene expression library is a useful method for the study of gene expression. Through the analysis of expression library, we can get the expression information of almost all genes and find out their alterations compared with other related libraries. Also, in expression library, we can analysis the interaction of gene expression, find new tumor markers, new gene expression even new genes, explore the etiopathogenesis and treatment methods of tumor. The technique of serial analysis of gene expression (SAGE) is a powerful method to construct expression library, which was engineered by Velculescu in 1995. The technique has been widely used in the research of tumor because it can find new genes. Two SAGE libraries of colon cancer had been constructed in the U.S.A. in 1996. But no SAGE libraries of Chinese colon cancer have been constructed yet. The objective of our research was to construct the SAGE libraries of Chinese adenocarcinoma and normal mucosa of colon. And to explore the characteristics and difference of gene expression in Chinese adenocarcinoma and normal mucosa of colon compared with related libraries. These would offer important clues for further studies.Methods:The gene expression libraries of adenocarcinoma and normal mucosa of colon were generated by the technique of serial analysis of gene expression. Some clons were selected and sequenced. The expression tags were gained from the sequencing results by using of the SAGE2000 software. The representing genes of tags were gained in the Sagemap offered by NCBI. The highly expressed genes were selected and their expression in different libraries was compared using the SPSS13.0 software.Results:1. From the SAGE libraries of adenocarcinoma and normal mucosa, 233 and 250 clones were selected and sequenced. 7672 and 7926 tags were gained from the sequencing results by using of the SAGE2000 software. The average tags gained from every sequencing result were 32.9 and 31.7.2.3981 kinds of tags were found in the library of colon cancer. Among them, 3151 kinds only expressed once, 445 kinds expressed twice and the other 385 kinds expressed three times or more. In the library of normal mucosa, 3823 kinds of tags were found. 2923 kinds of them only expressed once, 470 kinds expressed twice and the other 430 kinds expressed three times or more.3. The 25 tags that most highly expressed in normal mucosa represented 36 different genes. 2 of them were found to express only in normal mucosa. 23 of the genes had decreased expression in cancer(P< 0.01) and the expression of the other 11 genes showed no significant difference between the two tissues. In cancer, the 25 tags that most highly expressed represented 38 different genes. Compared with normal mucosa, the expression of 32 genes showed increased (P <0.01) , 1 showed decreased (P<0.01) and the other 5 showed no significant difference.4. Many genes that participate in the metabolism of nucleonic acid or cell cycle controling had significantly different expression between cancer and normal mucosa.5. 101 kinds of ribosomal protein (RP) genes or similar to RP genes expressed in cancer or normal mucosa.6 kinds of them only expressed in normal mucosa, 17 kinds only in cancer and 78 kinds in both tissues. In the 58 kinds of RP genes expressed more than 10 times in cancer and normal mucosa, 41 kinds had significantly higher expression in cancer(P<0.01), the expression of others showed no significant difference between the two tissues.6. There were 1251 kinds of tags had no representing genes in Sagemap. 54 of them had expression in both tissues. In the 14 kinds of tags expressed more than 10 times in cancer and normal mucosa, 6 of them had different expression between the two tissues (P<0.01) .7.The expression of the 38 genes represented by the 25 tags expressed most highly in cancer had significantly lower expression in the SAGE libraries of Tu102 and Tu98 (P<0.01) .Conclusions:1. Most genes expressed in cancer and normal mucosa of colon showed a low level expression.2. The highly expressed genes in normal and cancerous tissues were significantly different. Further study on these genes, which had different expression between the two tissues, would find new tumor markers possibly and offer clues for the study on etiopathogenesis of colon cancer.3. Compared with normal mucosa, the expression of many genes related to cell cycle controling or metabolism of nucleonic acid had increased or decreased in colon adenocarcinoma. These genes may have important effect on the genesis and development of colon cancer.4. The expression of RP genes was different between cancer and normal mucosa. Many RP genes had increased expression in cancer and may be important agents to result in the genesis and development of colon cancer.5. The highly expressed tags in SAGE library of Chinese colon cancer had lower expression in foreign libraries. The genesis and development of Chinese colon cancer may have its own characteristic.
Keywords/Search Tags:Serial analysis of gene expression, colon adenocarcinoma, colon normal mucosa
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