| Background & Objective:Lung cancer is one of the most common malignant tumors, whose morbidity and mortality are increasing gradually, and become the main cause of death in most of the countries. In recent years, with the improvement of knowledge about lung cancer and development of moleculary biology, people have done a large number of basic and clinic studies in the occurrence and development, diagnosis and therapy of lung cancer. The 5 year survival rate of lung cancer is less than 15% although advance in surgery, chemotherapy and radiation. The occurrence and development of tumor is a multistage process involving alteration in multiple genes, and the imbalance of apoptosis plays an important role in this process. In recent years, the research in function of apoptosis-related genes to tumor has become a hot spot, and the therapy aiming at these genes is probably a new therapy tool of cancer. The programmed cell death 5 is a new aopoptosis-related gene cloned in the human disease center of Peking University. The PDCD5 has the function of tumor inhibition, and plays an important role in the development of cancer. Furthermore it has been reported that the expression of PDCD5 is down-regulated and even deleted in some kinds of malignant tumors, such as leukemia, ovarian, prostate, gastric and breast cancer. However the expression of PDCD5 on lung cancer has been rarely reported at home and abroad. The aim of this study is to test the expression of PDCD5 in lung cancer, analyze the correlation of PDCD5 with clonicopathological characteristics and prognosis of lung cancer patients, and then investigate the role of PDCD5 in the development of lung cancer..Methods:71 non-small-cell lung caner tissues including lung squamous cell carcinomas and adenocarcinoma tissues were obtained from patients who underwent lung cancer resection in Provincial Hospital affiliated to Shandong University. At the same time,15 adjacent normal lung tissues were obtained from the region farther than 5 cm to the cancer tissue edge. All the patients had not underwent any adjuvant treatments, such as chemotherapy, radiotherapy and biotherapy before the surgery in order to eliminate their effects on gene expression. All 86 specimens were examined by immunohistochemistry to detect the expression of PDCD5 protein, and test the expression of PDCD5 in 3 fresh adjacent normal lung tissues and 5 lung cancer tissues by western blot. Input all data to SPSS software to establish a database to analysis. The chi-square test was used to compare the PDCD5 protein expression in groups with different clinicalpathological characteristics. Kaplan-Meier method was performed to estimate the 5-year survival rate. Compare the survival between different PDCD5 expression groups used Log-rank test. Investigate the independent prognostic factors of lung cancer by Cox regression multivariate analysis.Results:Immunohistochemical results showed that 26(36.6%) of 71 non-small-cell lung cancer tissues was high for PDCD5 expression,45 lung cancer tissues was low for PDCD5 expression, all 15 normal lung tissues was high for PDCD5 expression, and there was a significant difference between them(X2= 19.942, P<0.001). Compared the PDCD5 expression between different clilial stage groups, we found that PDCD5 protein expression gradually reduced as the clinical stage increasing (X2=31.887, P<0.001). The expression of PDCD5 was gradually reduced as the differentiation degree decreasing, and there was also a significant difference between them (X2=7.249, P<0.05).However, no significant correlation with gender, age, smoking, family history and clinical pathological types was demonstrated for PDCD5 expression. Western blot results showed that the PDCD5 in 3 normal lung tissues were all high-expression, while the PDCD5 expression in 5 lung cancer tissues declined obviously and even missing. The overall 5-year survival rate of these lung cancer patients was 38.0%. Furthermore, the 5-year survival rate in patients with high expression of PDCD5 protein was significantly higher than those with low expression(X2=18.599,P<0.001). The results of Cox regression single factor analysis showed that pTNM stage, smoking, differentiation degree and PDCD5 protein expression were significant influencial factors of the overall 5-year survival in lung cancer patients(P <0.05). The results of Cox regression multivariate analysis confirmed that PDCD5 protein expression(RR=0.377, P=0.028) and pTNM stage(RR=3.844, P=0.001) were independent prognostic factors.Conclusions:The results of immunohistochemical test and western blot suggested that PDCD5 expression was significantly low in lung cancer tissues, compared with normal lung tissues. The PDCD5 may be a kind of tumor surppressor genes of lung cancer, its low expression and deletion probably plays an important role in the occurrence and development of the lung cancer. The PDCD5 expression was closely associated with pTNM stage and differentiation degree, but had no relation to other clinicalpathological characteristics such as age, gender, smoking, family history and clinical pathological types. The relationship between the PDCD5 protein expression in lung cancer and the prognosis of patients suggested that the 5-year survival rate of patients with PDCD5 high expression was significantly higher than the patients with PDCD5 low expression. The level of PDCD5 expression is an independent prognostic factor in lung cancer patients. PDCD5 might become a potential molecular marker of early diagnosis and new target of clinical treatment of lung cancer. |
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