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The Expression Of Notoh Signal And Its Significance In Non-small-cell Lung Cancer

Posted on:2011-08-23Degree:MasterType:Thesis
Country:ChinaCandidate:B YangFull Text:PDF
GTID:2144360305454806Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Lung cancer showed a significant increase in the incidence and mortality trends both in China and around the world. Lung cancer can be divided into two major categories, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the incidence of NSCLC accounts for 80-85%. In recent years, surgery, neoadjuvant chemotherapy and other treatment methods have greatly improved, but the 5-year survival rate of NSCLC patients have not been significantly improved. With the development of molecular biology techniques, and the further understanding of the molecular mechanisms of NSCLC, molecular targeted therapy of NSCLC gets more and more attention.Notch signaling pathway was originally discovered in Drosophila, and was found widely expressed from invertebrates to mammals. Notch signaling pathway is highly conserved during evolution. it plays an important role in the process of embryonic development and cell fate decisions. The role in human tumour genesis became apparent when it was found that the Notch1 receptor gene was engaged in chromosomal translocations in a subset of T-cell acute lymphoblastic leukaemias (T-ALL). Then later research shows that, both hematopoietic tumors and a variety of solid tumors are associated with the abnormalities of Notch signaling pathway. The molecular therapy targeting to Notch pathway is a potential experimental approach to cancer treatment. Currently, mainly studies on the role of Notch signaling pathway in the occurrence of NSCLC, are based on the observation with gene expression of Notch receptor and its downstream in the cultured cell lines, witch can not clearly showed the expression of Notch signaling pathway in lung tissue.We chose 42 cases of non-small cell lung cancer specimens by surgical resection in chest surgery department of the First Hospital of Jilin University. All the cases were proved by pathological diagnosis after opertation. 12 cases normal lung tissue were taken as control group. All specimens were put into liquid nitrogen immediately after operation . We detect the expression level of Notch receptor and ligand mRNA by RT-PCR. We aim to explore the relationship between Notch signaling pathway and NSCLC, to reveal molecular mechanism of Notch signaling pathway during the development of NSCLC and to provide a new target for targeted therapy of NSCLC.The positive expression rate of Notch1 mRNA in NSCLC tissues was significantly higher than that in normal lung tissues (P<0.05); The positive expression rate of Notch1 mRNA was no significant difference between squamous cell carcinoma and adenocarcinoma (P>0.05); The positive expression rate of Notch1 mRNA in patients with lymph node metastasis was significantly higher than those without (P<0.05).Notch2 mRNA expressed in all NSCLC tissues and normal lung tissues, the expression in the former was significantly higher than that in the latter (p<0.05); The expression of Notch2 mRNA was no significant difference between squamous cell carcinoma and adenocarcinoma (P>0.05); The expression of Notch2 mRNA was no significant difference between patients with lymph node metastasis and those without (P>0.05)The positive expression rate of Notch3 mRNA was no significant difference between NSCLC and normal lung tissues (P>0.05). The positive expression rate of Notch3 mRNA was no significant difference between squamous cell carcinoma and adenocarcinoma (P>0.05); The positive expression rate of Notch2 mRNA was no significant difference between patients with lymph node metastasis and those without (P>0.05)The positive expression rate of Jagged1 mRNA in NSCLC tissues was significantly higher than that in normal lung tissues (P<0.05); The positive expression rate of Jagged1 mRNA in adenocarcinoma was significantly higher than that in squamous cell carcinoma (P<0.05); The positive expression rate of Jagged1 mRNA in patients with lymph node metastasis was significantly higher than those without (P<0.05).Delta1 mRNA expressed in all NSCLC tissues and normal lung tissues, the expression in the former was significantly higher than the latter (p<0.05). The expression of Delta1 mRNA was no significant difference between squamous cell carcinoma and adenocarcinoma (P>0.05); The expression of Delta1 mRNA was no significant difference between patients with lymph node metastasis and those without (P>0.05)In summary, there are a certain correlation between Notch signaling pathway and the occurrence of NSCLC. The positive expression rate of Notchl, Jagged1 mRNA in NSCLC were significantly higher than that of normal lung tissues; The expression of Notch2, Delta1 mRNA in NSCLC were significantly higher than that in normal lung tissues, it showed a certain degree of correlation between Notch1, Jagged1, Notch2, Delta1 and the occurrence of NSCLC. There were not obvious correlation between Notch3 and the occurrence of NSCLC. The positive expression rate of Jagged1 mRNA in adenocarcinoma was significantly higher than that in squamous cell carcinoma, it showed closely correlation between Jagged1 and adenocarcinoma. The positive expression rate of Notchl, Jagged1 mRNA in patients with lymph node metastasis was significantly higher than those without, showed that may promote the development of NSCLC. Blocking Notch signaling may play an important role in the molecular targeted therapy of NSCLC.
Keywords/Search Tags:Non-small cell lung cancer, Notch signaling, RT-PCR
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