Analysis Of Relationship Between E-cadherin Gene And Nm23 Gene And Postoperative Prognosis And Lymph Node Metastasis Of Non-Small Cell Lung Cancer

Lung cancer is one of the most common malignant carcinoma with high mortality and morbidity in the word wide.The area of the developing countries in which is of highest morbidity of lung cancer is East Asia,while the second one is China.In the early of this century,lung cancer is still very rare in the whole world.But as following,especially after the middle of this century,initially in the developed countries,then the developing countries,the mortality and morbidity are increasing rapidly.At this moment,lung cancer takes the first place in malignant carcinoma of male,second and third of women's in most developed countries.From 40's to 80's in USA,the morbidity of lung cancer of man has increased 22.5 times,from 2.7 per 100,000 to 89 per 100,000 people,increasing 3%by average.But since 1984,owing to the campaign of "giving up smoking",there is no increase in the morbidity of lung cancer.During the same time,the situation for women is that the number of female lung cancer patients still increased from 7 per 100,000 to 35 per 100,000 people,and is continually increasing.Since 1987,the number of the female patients dead of lung cancer has got bigger than that of breast cancer,and lung cancer has taken the first place among the malignant carcinomas which lead to death.From 1950 to 1980 in Japan,the mortality of lung cancer increased 10 times for men and 7.5 times for women.It is assumed that in the end of this century,lung cancer will be the first or second common tumor in most developed countries and others.According the statistic data of ACS (American Cancer Society),in 1998,lung cancer was responsible for 28%to 29%death of cancer in US.As a result,it has already become a great threat to health and life of human being.Till 2005 in China,the morbidity of lung cancer for men's is 49.0/100,000 and 22.9/100,000 for women,moreover,the number of patients with lung cancer has increased 120,000. There are 4 characteristics for the epidemiology of lung cancer as follows:Lung cancer has become the one of the most common diseases,there are more than 600,000 people who die of lung cancer every year.In Beijing,the mortality and morbidity of lung cancer is ranked as the first among all the malignant carcinoma.Among the patients with lung cancer,male patients are the most then the female.While the mortality of lung cancer both for male and female is the No.1 in all carcinoma.Urbanization and aging.The data of whole country shows that,the morbidity and mortality no matter in domestic and abroad are both different in city and countryside.The ratio is higher in city than suburb and countryside,more in big cities than in small ones,more in industry zones in big cities. There is a obvious trend that more and more patients with lung cancer are young people and female.According to the recent data of UICC(International Union Against Cancer),the morbidity-age curve of lung cancer is prone to move forward,the average age of the patients with lung cancer is 5 to 10 years younger than before.For example,in 70's in Beijing,it mostly happens in age of 60 years old,but it increased rapidly to 50 years old in 80's,and at the end of 90's,even in the age of 40's.It is in almost all the countries and areas that the morbidity and mortality of lung cancer in male is much higher than in female. 4.The environment is also a factor leading to lung cancer.A famous oncologist named Peto from England predicted that if there were no a in time control for the smoking and air pollution in our country,by the year of 2025,the number of patients with lung cancer will exceed 1 million,then our country will become the largest country with lung cancer patients in the world.The overall of 5-survivals of lung cancer patients was less than 15%by the lack of early diagnosis and effective methods of therapy.Therefore it's very important to research molecule pathogenic mechanism of lung cancer.To investigate the expression of nm23 and E-Cadherin in non-small cell lung carcinoma(NSCLC),and their relationship with lymphoid metastasis and prognosis.To detect the level of E-cadherin gene and nm23 gene mRNA in human non-small cell lung cancer(NSCLC),and to study the relationship between expression and clinicpathologic features and prognosis.To investigate the role of E-Cadherin gene and the nm23 gene mutation in non-small cell lung carcinoma(NSCLC). The expression level of nm23 and E-Cadherin was detected in 138 patients with non-small cell lung cancer and 20 normal lung tissue as controls by immunohistochemistry methods.RT-PCR was used to measure the level of E-cadherin mRNA and nm23 mRNA expression in 59 specimens of NSCLC,46 of para-cancer lung tissues,5 of benign nodal lung diseases,and the stages of disease was determined according to the results of surgery, pathology and imaging diagnoses.Then analyses were carried out between the level of E-cadherin mRNA and nm23 mRNA expression and the clinical variables.Polymerase chain reaction—single strand conformation polymorphism(PCR-SSCP) was employed for mutational analysis of the nm23 gene and E-Cadherin gene in 53 surgically resected lung cancer and 5 normal pulmonary tissues.The expression level of nm23 and E-Cadherin was detected in 138 patients with non-small cell lung cancer and 20 normal lung tissue as controls by immunohistochemistry methods.The expression level of nm23(71.23±5.19%) and nm23-H1(64.98±5.72%) in the lung cancer tissue was significantly lower than that in the para-cancer lung tissues (89.00±7.21%)(P＜0.05) and normal lung tissue(90.66±6.78%)(P＜0.05).The expression level of nm23 gene and nm23-H1 was closely related to cell differentiation,progression and prognosis of lung cancer(P＜0.05).Three-year and 5-year survival rate of patients with high nm23-H1 expression(78.81%,55.73%,respectively) was significantly higher than those with low nm23-H1 expression.The Cox proportional hazard regression mode revealed 4 important factors pertaining to patient survival rate as following:nm23-H1expression level,TNM stages,lymph node metastasis and size of primary tumor.The expression level of E-cadherin(41.48%) was obviously lower than that in Normal lung tissue(73.12%)(P＜0.05).The degree of expression level of E-cadherin was closely related to metastasis of lung tumor but not obviously related to cell differentiation,tumor size,histology types,and smoking(P＞0.05).Five-year survival rate of patients with high E-cadherin expression(＞40%) was significantly higher than those with low E-cadherin expression(≤40%)(51.43%,21.67%,respectively)(P＜0.05).Among these patients whose age ranged from 29 to 78 years,40 were males and 13 were females,and the average age was 58.28±9.38 years.The types of tumor were involved:squamous cell carcinoma(34.0%,18/53),adenocarcinoma(45.3%,24/53), bronchioalveolar carcinoma(3.8%,2/53),adeno-squamous carcinoma(17%,9/53). Differentiation degree:1 grade and 1-2 grade were well-differentiated(45.3%,24/53);2-3 grade and 3 grade were poorly differentiated(54.7%,29/53).Pathologic stage:Ⅰ(26.4%,14/53),Ⅱ(24.5%,13/53),Ⅲ(43.4%,23/53),Ⅳ(5.7%,3/53).All cases were not carried out of radiotherapy and chemotherapy before operation.It's no significant difference in the expression level of nm23 and E-Cadherin mRNA between cancer lung tissues,para-cancer lung tissues and normal lung tissue by RT-PCR.We discoveed that the expression level of nm23 and E-Cadherin mRNA of well-differentiated,earlier stage and unmetastatic lymph nodes in cancer lung tissues were significantly higher than that of poorly differentiated,advanced stage and metastatic lymph nodes through quantitative analysis(P＜0.05or 0.01).The outcome of follow-up showed that the expression level of nm23 and E-Cadherin mRNA was no significant correlation with prognosis in human non smal cell lung cancer(P＞0.05).Among of 53 cases,the four types of tumor were involved namely,squamous cell carcinoma(41.51%,22/53),adenocarcinoma(33.96%,18/53),bronchioalveolar carcinoma(9.43%,5/53),adeno-squamous carcinoma(15.09%,8/53).Pathology stage:Ⅰa (9.43%,5/53),Ⅰb(15.09%,8/53),Ⅱa(7.55%,4/53),Ⅱb(32.08%,17/53),Ⅲa(26.42%,14/53),Ⅲb(7.55%,4/53),Ⅳ(1.86%,1/53).There were no metastatic lymph nodes in 17 cases. There were homonymy of metastatic hilar lymph nodes in 21 cases.There were homonymy of metastatic mediastinum lymph nodes in 14 cases.There were opposite side of metastatic mediastinum lymph nodes in one cases.Five other cases were harmatoma, inflammatory pseudotumor,neurosarcoma and two carcinoids.There were mutation E-cadherin gene in three cases.We did not found mutation nm23 gene in 53 cases.There was no mutation in non-lung cancer tissues.It's no significant difference in mutation E-cadherin gene between cancer lung tissues and non-cancerl lung tissue.The mutation E-cadherin gene was correlation with the status of lymph node metastasis.The more N stage,the more rate of mutation of E-Cadherin gene.But its mutation was not relation with pathology type and the status of primary tumor(P＞0.05).However the mutation of nm23 was not relation with pathology type,lymph node metastasis and the status of primary tumor(P＞0.05) The outcome of follow-up showed that the mutation of nm23 and E-Cadherin was no significant correlation with prognosis in human non smal cell lung cancer(P＞0.05).From the above-mentioned results,we concluded that nm23 gene and nm23-H1 gene suppressed tumor metastasis in NSCLC and the decrease in their expression may be one of the essential causes of lung cancer metastasis;the expression of E-Cadherin was negative correlation with TNM stages of NSCLC.The expression level of E-Cadherin could be considered as biological parameter of prognosis in NSCLC;The expression of nm23 and E-Cadherin mRNA could be better predicted that differentiation degree,pathologic stages and the status of lymph nodes metastasis.,but were not significant correlation with prognosis and other clinic feature of pathology;The E-Cadherin gene could be better predicted the status of lymph nodes metastasis in NSCLC,however it's very rare to found the mutation of nm23 gene and hard to determine it correlation with non-small lung cancer carcinogenesis and clinic feature of pathology.