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Expression Of Apoptosis-associated Genes TRAIL And Bcl-2in Human Non-small-cell Lung Cancer And Its Clinical Significance Study

Posted on:2013-01-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y ZhengFull Text:PDF
GTID:2234330371977103Subject:Geriatrics
Abstract/Summary:PDF Full Text Request
1AimsLung cancer is the primary in the lungs the serious harm is harmful to human health and human life of malignant tumor, worldwide, it is the leading cause of cancer death the main reason1(Jemal et al.,2007), the mortality rate in our country city has in the malignant tumor.. In many countries of the world lung cancer has been the most common malignant tumor, in South Korea, lung cancer has beyond stomach cancer into cancer’s leading cause of death1-2[1,2]. Of newly diagnosed non-small cell lung cancer cases about35-40%of patients for the small cell type and the small cell lung cancer locally advanced (non-small cell lung cancer)3[2], especially old people is the high-risk groups. In recent years a number of research shows that lung cancer by cell proliferation and differentiation abnormalities, namely former cancer gene to be activated, tumor suppressor genes in cells within the deactivation group live and death of balance is destroyed, still with abnormal cell apoptosis related.TRAIL is tumor necrosis factor-related apoptosis-inducing ligand, Bcl-2gene (namely B cell lymphoma/leukemia-two genes) is a former cancer gene. Research shows that TRAIL is a kind of promote apoptosis genes, and Bcl-2is one of apoptosis or genes. This experiment through research and Bcl-2TRAIL apoptosis related gene in non-small cell lung cancer (NSCLC) and the correlation expression, to explore the TRAIL, Bcl-2biological significance and the clinical the pathogenesis of NSCLC, for the early diagnosis and treatment NSCLC to provide the basis.2Object and Methods2.1Object of studyCollect in January2009-2011years between November of zhengzhou university first affiliated hospital of the department store thoracic surgeries resection and confirmed by pathology for NSCLC of lung cancer tissue samples from60cases for the test group, at the same time as control group is20cases by the lung cancer NSCLC normal (that is, more than3cm from the tumor edge and confirmed by pathology for normal lung tissue); All of the lung cancer patients in preoperative all did not accept any antineoplastic therapy.2.2MethodsUsing immunohistochemistry methods were used (S-P method) test TRAIL, Bcl-2in the lung scale cancer, lung adenocarcinoma and normal lung tissue of the cancer expression; The apoptotic cells by TUNEL method detection, and calculation apoptosis index (AI).2.3Standards of decision outcomes2.3.1Standards of positive expression of TRAIL、Bcl-2At high magnification in vision (20x10), random choose five perspective in positive results of judgement, and every vision will have a positive cells, and each field of vision plan100cells, a total of500cells; TRAIL positive cells for the cell nucleus appear tan grain, Bcl-2positive cells for cytoplasm/the nuclei occur within a tan plan for particles, the nuclear no color; Judge method is:(1) score standard for positive cells percentage:0points:0%, one point:<10%,2points:10%-50%, and three points:>50%;(2) score standard for cell dyeing depth:no tan particles, and no difference in the background for0; Have yellowish-brown particles, much higher than the background for1minute; Have a clear dyeing of tan particles, between two points between strength for; There are a lot of dark brown grain, dyeing strong as three points; Dyeing strength and positive cells as a percentage of comprehensive judgment, namely (1) and (2):final score frequency is divided into four express positive (+),<4divided into express negative.2.3.2Assessing apoptosis cell and calculating Apoptotic IndexTest method with TUNEL apoptotic cells, the apoptotic cells for the nuclei dyed tan cells; Apoptosis index (AI) calculation:in at high magnification (40x10) randomly selected10view, the calculation of the apoptotic cells and the ratio of the total count cells, namely AI=the apoptotic cells x100%total number/cells.Application software SPSS17.0statistical data analysis; Statistical methods:a chi-square test, matching the relevance of data analysis, chi-square calibration and the continuity of the linear correlation analysis to a=0.05for inspection standards.3Results3.1The expression of TRAIL in normal lung tissue and NSCLC, and its relation of clinical path-charaterTRAIL mainly express to normal lung tissue epithelial cells, NSCLC cell cytoplasm also have expressed, but significantly weaker than normal dyeing strength lung tissue, positive cells number also obviously less than normal lung tissue, dyeing as light yellow to tan.60cases in the positive TRAIL NSCLC organization expression rate is45.0%(27/60),20cases of normal lung tissue positive expression rate was60.0%(12/20), the difference was statistically significant (the chi-square=13.144, P=0.000). TRAIL in NSCLC well-differentiated groups express the positive rate was60.0%, the middle and low differentiation groups express positive rate was18.0%, the difference was statistically significant (the chi-square=5.760, P=0.016). TNM staging Ⅰ, Ⅱ period of positive expression rate was38.9%, the III, IV period of positive expression rate was4.2%, the difference was statistically significant (the chi-square=9.259, P=0.002). TRAIL in a lymph node metastasis in patients with NSCLC positive expression rate is3.7%, without lymph node metastasis to express the positive rate was42.4%, the difference was statistically significant (the chi-square=11.874, P=0.001). The expression of the TRAIL with NSCLC patients age, gender, tumor diameter, pathology classification, smoking, and presence of pleural transfer business.3.2The expression of Bcl-2in normal lung tissue and NSCLC, and its relation of clinical path-charater Bcl-2main role in the cytoplasm or the nuclei.60patients with NSCLC organization Bcl-2positive expression rate was68.3%(35/60),20cases of normal lung tissue positive expression rate was25.0%(5/20), the difference was statistically significant (the chi-squareX2=2.526, P=0.086). Bcl-2in NSCLC well-differentiated groups express the positive rate was10.0%, the middle and low differentiation groups express positive rate was54.0%, the difference was statistically significant (the chi-square=4.835, P=0.028). TNM staging Ⅰ, Ⅱ period of positive expression rate was33.3%, the III, IV period of positive expression rate was66.7%, the difference was statistically significant (the chi-square=6.429, P=0.011). Bcl-2in a lymph node metastasis in patients with NSCLC positive expression rate is74.1%, without lymph node metastasis to express the positive rate was24.2%, the difference was statistically significant (the chi-square=14.816, P-0.000). Bcl-2patients with NSCLC and the expression of the age, sex, tumor diameter, pathology classification, smoking, and presence of pleural transfer business.3.3The relation of TRAILandBcl-2in NSCLCThe relevance of matching material analysis, the conclusion TRAIL and Bcl-2in NSCLC tissue of expression some association, for negative correlation (the chi-square=8.929, P=0.003, r=0.386).3.4The relation of TRAIL and Bcl-2with apoptosisLinear correlation analysis, the conclusion TRAIL integral and apoptosis of index are positive correlated AI (r=0.663, P=0.000), Bcl-2points and apoptosis index AI a negative correlation (r-0.736, P=0.000).4Conclusion1. TRAIL, Bcl-two differentially expressed genes may be in NSCLC the occurrence and development of plays a role. TRAIL, Bcl-2is expected to become the new tumor marker.2. The TRAIL protein expression and lung cancer differentiation degree, TNM staging close relationship, TRAIL positive expression rate is lower, the higher the degree of malignancy NSCLC may; Bcl-2positive expression rate is high, the higher the degree of malignancy might NSCLC.3. Detection TRAIL, Bcl-2May contribute to the clinical TNM staging.4. Detection TRAIL, Bcl-2May help without lymph node metastasis judgment.5. And Bcl-2in the lung normal tissue low expression, high in lung cancer group expression, and in the lung squamous cell carcinoma of the organization expression rate was significantly higher than adenocarcinoma organization, and lung cancer closely histologic type, detection Bcl-2protein helps to lung cancer early diagnosis, organization, the formulation of treatment for type points and prognosis.
Keywords/Search Tags:TRAIL, Bcl-2, NSCLC, apoptosis, immunohixtochemisty
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