A Study For The Correlation Of GRIM-19 Together With Its Target Gene Product STAT3 To Lung Cancer

Background:The lung cancer is the most common malignant tumor in the world and is the main reason for the death because of cancer. So it is regarded as the biggest menace to people's health. Gene associated with retinoid- IFN- induced mortality-19 is one member of the GRIMS apoptosis-related gene family. It is a IFN-B new cells death control factor united with RA induced expression and discovered by Angell et al. with the method of antisense gene exclution. GRIM-19 is a kind of 16-kDa small nucleoprotein and distributes in nuclear and cytoplasm, located at human chromosome 19P13.1. It has been proved that the GRIM-19 is the composition of the purified mitochondria respiratory chain complex I. This complex is necessary for the generation of ATP. When the mitochondria complex's electron generates activity, GRIM-19 mutant breakthroughs mitochondrial transmembrane potential and strengthens the cells' sensitivity to apoptosis stimulation. Signal transducers and activators of transcription 3(STAT3) is one of the most important members of STAT family and takes part in many of cytokine responses. STAT3 signal transduction's stimulation can induce the cell abnormal proliferation and malignant transformation. It has been proved that the STAT3 plays an important part in tumor cells' generation, growth, and apoptosis inhibition. Research shows that the GRIM-19 can specific inhibition the STAT3's activity, promoting tumor apoptosis. GRIM-19 together with STATS can down-regulated cyclin,c-myc,Bcl-2,Bcl-XL down regulation target gene.Besides, STAT3 also promote gene expression of Bcl-2,Bcl-XL anti apoptosis mitochondria permeability regulation factor. GRIM-19 was found expression in many of the normal tissues, but with different distribution. It has been found that this expression is high in heart, skeletal muscle; liver, renal and placenta; while relatively lower in lung, circulating granulocytes, spleen, thymus and colon. But there has not been any report about this expression in lung cancer tissues.ObjectiveWestern blot was adopted to examine the expression of GRIM-19 protein and STAT3 protein in 37 cases of lung cancer samples and adjacent tissue from the pulmonary carcinoma patients. The protein expression and the clinic pathological coherent characteristics were also statistically analyzed.Method1. Detect GRIM-19 protein expression in 37 cases lung cancer and adjacent tissues using Western Blot analysisTotal protein was extracted from 37 cases lung cancer and adjacent tissues, respectively, and the expression of GRIM-19 protein was measured by Western Blot.2. Detect STAT3 protein expression in 37 cases lung cancer and adjacent tissues using Western Blot analysisTotal protein was extracted from 37 cases lung cancer and adjacent tissues, respectively, and the expression of STAT3 protein was measured by Western Blot. .3. Analyze the relationship between GRIM-19 protein in lung cancer tissues and clinicopathological features of patientsSet 37 cases GRIM-19 protein expression in lung cancer tissues according to sex, histological type, clinical staging, age and smoking index , lymphatic metastasis then Analyze the relationship between GRIM-19 protein in lung cancer tissues and clinicopathological features of patients.4. Analyze the relationship between STAT3 protein in lung cancer tissues and clinicopathological features of patientsSet 37 cases STAT3 protein expression in lung cancer tissues according to sex, histological type, clinical staging, age and smoking index , lymphatic metastasis then Analyze the relationship between STAT3 protein in lung cancer tissues and clinicopathological features of patients.5. Statistical methodThe gray level of each band is analyzed by professional image analysis software Image-Proplus. The data is denoted as x±s, and statistical analyzed by SPSS 11.5. The mean value of each two data arrays is t tested, and for multi data arrays, the mean values is analyzed through single factor analysis of variance. The association analysis is done through Pearson correlation test.Result1. GRIM-19 protein expression in lung cancer and adjacent tissues We detect the expression of GRIM-19 protein in all the samples. The protein expression of GRIM-19 in lung cancer group decreased significantly compared to the corresponding adjacent group, respectively.2. STAT3 protein expression in lung cancer and adjacent tissues We detect the expression of STAT3 protein in all the samples. The protein expression of STAT3 in lung cancer group were significantly higher than in its'adjacent tissues.3. The relationship between GRIM-19 protein expression and clinical and pathological parameters of lung cancer patients Set 37 cases GRIM-19 protein expression in lung cancer tissues as five groups according to histology, TNM stage, sex, age, smoking condition, lymphatic metastasis.the relative amount of GRIM-19 protein expression of stage I–II were significantly higher than those of stage III-IV. However, the expression of GRIM-19 was determined not to be associated with the patients'sex, age, smoking condition, histology, lymphatic metastasis.4. The relationship between STAT3 protein expression and clinical and pathological parameters of lung cancer patientsSet 37 cases STAT3 protein expression in lung cancer tissues as five groups according to histology, TNM stage, sex, age, smoking condition, lymphatic metastasis. The relative amount of STAT3 protein expression of stage III-IV was significantly higher than those of stage I–II. Meanwhile, the STAT3 protein expression of lymphatic metastasis group was higher than none of lymphatic metastasis group .However, the expression of STAT3 was determined not to be associated with the patients'sex, age, smoking condition, histology.5. Analysing the relationship between GRIM-19 protein expression and STAT3 protein expression.GRIM-19 expression in pulmonary carcinoma was negatively correlated to STAT3 expression (r=-0.327; P<0.05).ConclusionThe GRIM-19, which is a new trigger gene for the apoptosis, plays an important role in the generation and development of lung cancer, Along with further exploration of the mechanism of this apoptosis promotive effect, GRIM-19 can be the candidate for three possible applications: 1. to be a new tumor inhibitor; 2.to be a symbol for the therapeutic reaction. 3. to be the target point of gene therapy in case of exceptional expression.