Dissertation
Dissertation > Medicine, health > Oncology > Respiratory system tumors > Lung tumors

Expression of hnRNP A2/B1 and p21WAF1 Proteins in Lung Cancer and Their Clinical Significance

Author HanJun
Tutor LuYouJin
School Anhui Medical University,
Course Geriatrics
Keywords carcinoma,non-smallcelllung hnRNPA2/B1,P21WAF1 cell multiplication immunohistochemistry
CLC R734.2
Type Master's thesis
Year 2011
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Background:Lung cancer is the one of the most common malignant tumors in hunman, and is the main cause of cancer-related deaths. The pathogenesis of lung cancer is a multi-gene, multi-stage complex process, and the imbalance between cell proliferation and apoptosis is significantly involved of it. As a major RNA binding protein,a number of researches suggest hnRNPA2/B1 is also a very sensitive tumor-associated antigen. Metabolism of the cell cycle study found that A2 and B1 was mainly synthesized in the G1 phase, and tumor cells formed mainly in the G1 to S phase by transition disordered. P21WAF1 gene , one member of CDK inhibitor (CKI) Cip / Kip family, can inhibit CDK kinase activity, blocking cell G1 phase to S phase transition, thereby inhibiting cell proliferation.A large number of experiments suggested that hnRNPA2/B1 was involved in cell proliferation and the growth of transcriptional regulation. Recently, shRNA-induced knockdown of hnRNP A2 was used with DNA microarrays to identify downstream targets of A2, and founded its several downstream targets mediating cell growth. Further, negative regulatory factors of in p21 ubiquitin-dependent proteolysis was founded in the downstream genes, suggesting that the close relationship between the two genes.Recently, many studies have focused on the specific over-expression of hnRNP A2/B1 in non-small cell lung cancer. However, the correlation between the expression of hnRNP A2/B1 and the pathological type,tumor differentiation,lymph node metastasis and TNM stages of NSCLC patients has not been fully elucidated. The relationship between hnRNP A2/B1 and oncogenes, tumor suppressor genes and other apoptosis-related genes in lung cancer is not yet clarified. As a possible molecular marker of NSCLC, hnRNP A2/B1 may become a new target for diagnosis and treatment of NSCLC, and deservesmore attention.Objective:To detect the expression of hnRNP A2/B1 and P21WAF1 proteins in NSCLC tissues, paracanceious tissues and benigh pulmonary lesions tissues. To understand the role of the two proteins in NSCLC development by analyzing the correlation between them.The experiments base for Livin as lung cancer molecular markers used in clinical with be provided.Methods:The expression of hnRNP A2/B1and P21WAF1 proteins was detected by streptavidin-peroxidase immunohistochemistry method in 53 cases of NSCLC,40 paracanceious tissues and 7 benign pulmonary lesions tissues. Expression of these proteins was analyzed for correlation with histological typing, differentiation degree , clinical stage and lymph node metastasis. Results:The postive expression rate of hnRNP A2/B1 in NSCLC(66.0%) was significantly higher than those in paracanceious tissues(37.5%) and benigh pulmonary lesions tissues(14.28%)(P<0.05); The postive expression rate of P21WAF1in NSCLC (45.2%) was higher than those in paracanceious tissues (7.5%) and benigh pulmonary lesions tissues(0%). The postive expression rate of hnRNP A2/B1 and P21WAF1in NSCLC were associated with differentiation degree and lymph node metastasis(P<0.05),except for histological types and clinical stage(P>0.05).In NSCLC,a negative correlation were present between hnRNP A2/B1 and P21WAF1 protein expression(pearson=-0.468,p=0.001)Conclusion:1 The postive expression rate of hnRNP A2/B1 and P21WAF1in NSCLC were associated with differentiation degree and lymph node metastasis, except for histological types and clinical stage. It suggests that two proteins may play an important role in lung carinomas and its progression.2 In NSCLC ,a negative correlation were present between hnRNP A2/B1 and P21WAF1 protein expression. hnRNP A2/B1 protein may reduce cell cycle and promote cell proliferation by upregulating the expression of P21WAF1 protein, accelerating the normal cell malignant transformation, resulting in the occurrence of lung developmeng and progression

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