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Selection Of Specific Genes And Study On The Relationship Between CD25 Expression And EBV Infection Of NPC

Posted on:2006-07-15Degree:MasterType:Thesis
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:2144360182455543Subject:Pathology
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The development of malignancy is an extremely complex process, including various of genes alterations, such as mutation or deletion of normal genes, abnormal amplifiaction and expression of oncogenes. Malignant tumors deriving from different tissues and organs possess different histological and biological characteristics. There is difference on the expression of genes related to the development of tumors. Therefore, selection of specific genes of various tumors is of great significance to the diagnosis and treatment of the tumor.Nasopharyngeal carcinoma (NPC) is epithelial malignancy of nasopharynx, highly prevalent in provinces of southern China. The tumorigenesis of NPC is a multi-stage and multi-factor process. Infection of Epstein-Barr virus, chemocarcinogen and genetic predisposition are three major factors of NPC. Many oncogenes and anti-oncogenes correlate closely with NPC. such as BCL-2, Madm2, Ras, Rb and P53. Recently, cDNA microarray is widly used in the research of NPC. Many new genes related with the development of NPC have been selected. In our study, differential expressed genes related with NPC have been selected from the obtained gene profiles and references. cDNA microarray was made to analyse the gene profiles of NPC tissue, NPC cell lines 5-8F, 6-10B; lung cancer cell line A549; colorectal cancer cell lines LoVo, SW480; bladder cancer cell line T-24 and mammary cancer cell line MCF-7. Specific genes were selected and studied in order to offer guidance in the diagnosis and treatment of NPC.There are 32 genes coexpression in NPC tissue and all cancer cell lines, including 17 up-regulated ones, 15 down-regulated ones, and 48 differential expressed one; 120 genes of differential expression was found between NPC tissue and NPC cell lines, including 52 up-regulated ones, 57 down-regulated. Besides, 33specifec genes were found in colorectal cancer cell line LoVo, inclouding 25 up-regulated ones, 8 down-regulated ones.CD25 (IL-2R α ) exists on the surface of activated T lymphocyte, B lymphocyte and macrophage. It is the low affinity receptor of IL-2. IL-2 is the important factor of the immune system, which plays an important role in specific immunity.lt can resist cancer and activate the proliferation of lymphocytes. IL-2 can make lymphocytes Lymphokine activated killer cell with strong cytotoxicity, and activates TIL to perform the role of anti-cancer. But only when IL-2 bind with IL-2R on the lymphocytes membrance can it play its roles. Therefore, the detection of IL-2R can reflect the immune status. In many cancer patients' PBL and tissues, the expression of CD25+cells are down-regulated.In NPC tissue, there are plenty of tumor infiltrating lymphocytes in the stroma, including T lymphocyte, B lymphocyte, macrophage, NK cell and dendritic cell. There is a proportion of CD25+cell in TIL, but the report of in situ expression of CD25 in NPC is less. EB virus infection is one of the major factors of NPC. LMP-1 and EBNA-1 can increase the expression of CD25 in lymphoma cell lines.In our study, we used in situ hybridization (ISH) and immunohistochemical method to detect the expression of EBER-1 and CD25 in 66 NPC samples respectively. The samples include 3 keratinizing squamous cell carcinoma, 7 differentiated nonkeratinizing carcinoma, 56 undifferentiated carcinoma and 30 chronic inflammation of nasopharynx .The results showed that in 66 NPC samples, 56 were (+++) of CD25(84%), 9 were (++)(14%), one was (+). In chronic nasopharyngitis, 8 were negative, 14 were (+), the proportion is 74%, 3 was (++)(10%), 5 were (+++)(16%). ( x 2-test, P<0.001)96.97%(64/66) of NPC were EBER-1 positive. Both differentiated nonkeratinizing carcinoma and undifferentiated carcinoma were both positive. 2 of 3 keratinizing squamous cell carcinoma were negative, the other is positive. The stroma of NPC and nasopharyngitises were all negative.20 of 60(33.3%) NPC samples, the mucosa were EBER-1 positive which was near the nest of cancer. 11 of 20 were the normal mucosa were EBER-1 positive, 9 of 20 were atypical hyperplasia were also EBER-1 positive. Meanwhile, 49 NPC theexpressed intensity of EBER-1 were (+++)~ (++++), 45 of them the expressed intensity of CD25 were (+++), the difference was significant (P<0.001).Our results confimed that there was higher expressed intensity of CD25 in NPC than nasopharyngitis. EBER-1 expresses in cancer cell, normal mucosal epithelia and atypical hyperplasia. It confirmed that EBV can infect normal epithelia of nasopharynx, which was involved in every stage of carcinomatous changes. The infection of EBV can enhance the expression of CD25 in NPC.
Keywords/Search Tags:Nasopharyngeal carcinoma, Microarray, EB virus, EBER-1, CD25
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