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The Expression Of RYR1in Non-small Cell Lung Cancer And Its Clinical Significance

Posted on:2013-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:J M ChenFull Text:PDF
GTID:2234330371474784Subject:Oncology
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[BACKGROUND] The tumor incidence is a process of gradual evolution, which the cells turn to malignant through a series of progressive change. With the rapid development of molecular biology, the cancer research enter the molecular and genetic level.It is To improve the patient’s survival time and quality of life to provide a new target to early diagnosis, early treatment and gene therapy for many tumors. The morbidity and mortality of lung cancer is the highest in all malignant tumors, occupying12.4%of all tumors, the quality of life is very poor, the5-year survival is less than15%. But the early diagnosis, early treatment of lung cancer is always the challenge for clinicians, Song Zhi-ming reported that80%of patients with lung cancer be diagnosed is to late, had lost the opportunity of surgical treatment.Some study reported that gene RyRl associate with many cancers, prompting that gene RyRl associate with the value-added and apoptosis of cancer cells. In this study, using real-time fluorescence Quantitative PCR technology to study PCR to study the gene RyRl to explore the relationship of gene RyRl and lung cancer.Ryanodine receptor1(RyRl) is a high molecular weight tetramer calcium channel protein, which is transcripted and translated from gene RyRl.It is an allosteric protein regulated by a variety of physiological factors and pharmaceutical preparations,three subtypes (RyRl-3) be found in vertebrates. The RyR subtypes showed different calcium sensitivity, and they own their feature of distribution in defferent tissue: the RyRl type distributed in the terminal pool of sarcoplasmic reticulum of skeletal muscle cells, it play a crucial role in thecalcium signal generation and myocyte excitation-contraction. RyR2is distributed mainly in myocardial, RyR3is distributed in brain and nerve tissue Ryanodine receptor1is regulated by agonists and antagonists to cause calcium concentration change, triggering calcium signals. The effect of this signal change in the muscle cells is to cause the skeletal muscle dysfunction.And in non-excitable cells,this calcium changing will cause corresponding change in the cell differentiation, proliferation and apoptosis. Some studys had reported that gene RyRl associate with the cells’proliferation and apoptosis in a variety of cancer cells. And there is few study about RyRl in lung cancer. This experiment is Expected to provide a new ideas for the early diagnosis of lung cancer.(OBJECTIVE} This experiment was to investigate the relationship of gene RyRl and lung cancer, investigating the relationship of the gene RyRl mRNA level with gender, age, pathological types,clinical stages and prognosis in lung cancer patients.[METHODS] Using SYBR Green I real-time fluorescence Quantitative PCR technology to detect the RyRl mRNA expression level of lung cancer(n=113),lung benign tumor(n=30) and adjacent tissues(n=55). The statistical software that we use is SPSS13.0software. The statistical methods we used T-test for two sample means’ comparision, LSD-t test for multi-sample means’comparision, ROC curve and excel for Calculating the best diagnostic cutoff value, Kaplan-Meier method for survival curve and the median survival time,and Cox Regression Model for multi-factors’analysis.[RESULTS](1)The result show that the RyRl mRNA expression level mean and Std.Deviation of the cancer tissue was0.2599±0.0562; the benign tumor was0.2070±.0455and the adjacent tissues was2242±0511. The mean difference of the comparison in the three tissues was significant(F=15.915,P=0.000). The means difference of the comparison between cancer tissue and benign tumor was significant (p=0.000); The means difference of the comparison between cancer tissue and adjacent tissues was significant (p=0.000); the difference the means comparison of the three means cancer tissue and adjacent tissues was not statistically significant (p=0.654).(2)The means difference of the comparison of gene RyRl mRNA level in different clinical stages’lung cancer tissues was significant (F’=8.738, p=0.000). The means difference of the comparison of gene RyRl mRNA level between the group of clinical stage I and group of clinical stage II was significant (P=0.006); the means difference of the comparison of gene RyRl mRNA level between the group of clinical stage I and group of clinical stage III was significant (P=0.024); the means difference of the comparison of gene RyRl mRNA level between the group of clinical stage Ⅱ and group of clinical stage III was not significant (P=0.237).(3)The RyRl mRNA level was no relationship with gender, age and pathological types, their p-values were all greater than0.05.(4)The best diagnostic cutoff value(0.207) was analyzed by ROC curve and excel. The median survival time of gene RyRl-positive patients was21.9months, the negative was39.3months, the difference was significant (P=0.000).(5)The multi-factor analysis by Cox proportional hazards regression model showed that the prognosis of patients with lung cancer is no relationship with gender, age, pathological types and chemotherapies, the p-values of their regression coefficients were all greater than0.05.But the regression coefficient of lymph node metastasis was1.370(p=0.008), of clinical stages was1.018(p=0.000) and of the expression of RyRl mRNA was0.992(p=0.001); three p-values were all lower than0.05.So lymph node metastasis,clinical stages and RyRl mRNA were the independent risk factors for the prognosis of patients with lung cancer[CONCLUSION](1) The RyRl mRNA level of lung cancer tissue was higher than benign tumor tissue and adjacent tissue; there was no differences between benign tumor and adjacent tissues(2) The RyRl mRNA level was no relation with gender, pathological type and age.(3) The RyRl mRNA level of the group of clinical stage I is lower than clinical stage Ⅱ and linical stage Ⅲ.(4) Lymph node metastasis,tumor stages, and the RyRl mRNA were all independent risk factors for lung cancer patients’survival time.
Keywords/Search Tags:Cells Apoptosis, Lung cancer, RyR1mRNA, Real-timePCR
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