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Clinical Application Of The7th Edition TNM Staging System For Lung Cancer And Expression Levels And Clinical Significance Of ROCK2in Non-Small Cell Lung Cancer

Posted on:2013-02-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:F Y FengFull Text:PDF
GTID:1264330401455901Subject:Oncology
Abstract/Summary:PDF Full Text Request
Lung cancer is the leading cause of cancer-related death in the world. Until effective systemic therapy is available for this disease, development of new treatment strategies depends on knowledge of the end results achieved for carefully staged groups of patients in the lung cancer population. Clinical stage is based on all of the available information obtained before a surgery to remove the tumor. Thus, it may include information about the tumor obtained by physical examination, radiologic examination, and endoscopy. Pathologic stage adds additional information gained by examination of the tumor microscopically by a pathologist. The7th edition lung cancer staging system has been widely used since2010.A total of1024lung cancer patients (1028lung tumors) operated in Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences during2010-2011were analyzed in this study. Restaging was done according to the6th and7th edition lung cancer staging system.In the present study, the comparison was done between the6th and7th edition TNM staging of1028lung tumors. For clinical TNM staging (cTNM), the overall concurrence rate was82.6%(849cases). When clinically staged with the7th edition TNM staging system,65tumors (6.3%) were up-staged and114tumors (11.1%) were down-staged compared to the6th edition system. For pathologic TNM staging (pTNM), the overall concurrence rate was78.3%(805cases). When pathologically staged with the7th edition TNM staging system,71tumors (6.9%) were up-staged and152tumors (14.8%) were down-staged compared to the6th edition system.The comparison was also done between the cTNM and pTNM staging of1028tumors with the7th edition TNM staging system. For T staging, the concurrence rate was66.6%(685cases), with clinically underestimated in6.8%(70cases) and overestimated in26.6%(273cases) of all tumors. For N staging, the concurrence rate was60.7%(624cases), with clinically underestimated in27.6%(284cases) and overestimated in11.7%(120cases) of all tumors. For TNM staging, the concurrence rate was50.7%(521cases), with clinically underestimated in23.7%(244cases) and overestimated in25.6%(263cases) of all tumors. It is indicated that the changes of TNM staging system resulted in the difference of the6th and7th edition staging of these1028tumors in this study. Furthermore, the limitation in accuracy of the existing physical examination, radiologic examination and endoscopy for clinical T and N staging may answer for the lower concurrence rate between the cTNM and pTNM staging with the7th edition TNM staging system. Lung cancer is the most common thoracic malignancies. Over2million new cases of lung cancer were diagnosed each year all over the world, among which non-small cell lung cancer accounts for more than85%, the worldwide burden of lung cancer is projected to rise considerably during the coming years. Advances in diagnosis and treatment of lung cancer have been made, but overall5-year survival rate remains to be lower than15%, and lung cancer remains the leading cause of death from cancer. The molecular mechanism underlying the development and progression of lung cancer remains to be unclear. It is still deserved great efforts to identify valuable molecular biomarkers with diagnostic and prognostic significance for lung cancer.ROCKs (including ROCK1and ROCK2) were initially identified as downstream target proteins of the small GTP binding protein RhoA, which belongs to the family of small GTPases. It was determined that ROCK protein could play an important role in the regulation progress of cell motility, proliferation and cell apoptosis. The most important role which ROCK proteins play is mediating the formation of RhoA induced stress fibres and focal adhesions. Increasing researches have demonstrated that ROCK proteins could be involved in many aspects of vascular disorders including abnormal vascular tone, endothelial dysfunction, inflammation, oxidative stress and vascular remodeling. For clinical treatment, inhibition of the Rho/ROCK pathway has been demonstrated to contribute to some of the cardiovascular benefits of statin therapy that are independent of lipid lowering. ROCK2was highlighted in our research for its former reported functions in tumorigenesis, for instance, high expression of ROCK2in hepatocellular carcinoma might contribute to the forming of the intrahepatic micrometastases while over expression of ROCK2in cervical cancer might promote the infiltration of tumor cells to the surrounding tissue. Expression levels of ROCK2in esophageal squamous cell carcinoma was found to be associated with differentiation degree. The expression of ROCK2in non-small cell lung cancer and its association with clinicopathological factors remained to be unclear.In this study, expression levels of ROCK2was determined in135cases of paraffin-embedded tissue samples from non-small cell lung cancer patients using tissue microarray (TMA) combined with immunohistochemical techniques, we found that ROCK2protein was located in the cytoplasm of non-small cell carcinoma cells. High expression rate of ROCK2in normal lung tissues was5.71%(6/105) compared with that of66.67%(90/135) in non-small cell lung cancer tissues, and the difference between these two groups had statistically significance (χ2=43.59, p<0.001). Furthermore, we investigate the relationship between the expression levels of ROCK2and the clinical factors of these patients such as age, sex, tumor location, smoking history, degree of differentiation and TNM staging in all of the135samples, no significant difference was found between the different groups of patients divided by theser clinical factors. Kaplan-Meier survival curve analysis indicated that5year survival rate of patients with higher ROCK2expression levels was lower than that of patients with lower ROCK2expression levels,38.89%versus57.78%, and the difference was statistically significant (Log-rank test, x2=5.085, p=0.024). Univariate Cox analysis showed that gender, smoking history, TNM stages, differentiation degree and ROCK2expression levels were statistically significant prognostic factors for non-small cell lung cancer patients. Multivariate Cox proportional hazards regression model analysis showed that TNM stage (p<0.001), differentiation degree (p=0.025) and ROCK2(p=0.009) expression levels were demonstrated to be independent prognostic factors for non-small cell lung cancer patients.In summary, our results demonstrated that ROCK2expression levels had special clinical significance for non-small cell lung cancer patients. ROCK2expression levels was associated with overall survival in non-small cell lung cancer patients, and turned out to be one of independent prognostic factors.
Keywords/Search Tags:lung cancer, staging system, clinical staging, pathologic staging, comparisonnon-small lung cancer, tissue microarray, immunohistochemistry, ROCK2
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