Expression Of GRIM-1 Protein In Non-small Cell Lung Cancer And Its Clinical Singnificane

BackgroundThe 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. In 2000, a report declared by WHO suggested that lung cancer, which has became the first malignant cause of death in man and the second in women, accounts for 19 percent in all malignant cancers. According to incomplete statistic, about 70 percent of lung cancer has been diagnosed in metaphase or advanced stages. They have lost the chance of surgeon. Genes associated with retinoid- IFN induced mortality are the GRIMS apoptosis-related gene family. They are IFN-βnew cells death control factors united with RA induced expression and discovered by Hofmann et al. with the method of antisense gene exclution.Gene associated with retinoid-interferon mortality-1(GRIM-1) is one of the death-related genes induced by retinoid-interferon. Over expression of GRIM-1 could suppress proliferation and promote apoptosis of tumor cells growth, enhance the sensitivity of cells to IFN-RA-induced death. SHQ1 was first discovered as a human counterpart to the yeast H/ACA RNP assembly factor shq1p. SHQ1 plays an important role in the biogenesis of H/ACA small nucleolar and telomerase RNPs. As researches on GRIM-1 expression in lung cancer tissues have not yet been reported both at home and abroad, In this study, We detected expression of GRIM-1 in 33 cases NSCLC tissues using Immunohistochemistry, and verified GRIM-1 protein expression levels using western blot. Analyzing the relationship between GRIM-1 protein and clinicopathological features, and to further explore the role of GRIM-1 in lung cancer carcinogenesis and the association with the development of lung cancer.ObjectiveIn the present study, we used lung cancer and adjacent tissues to investigate the expression of GRIM-1 and determine the cellular distribution of GRIM-1.Analyzing the relationship between GRIM-1 protein and clinicopathological features, and to further explore the role of GRIM-1 in lung cancer carcinogenesis and the association with the development of lung cancer.Methods1. The expression of GRIM-1 in lung cancer and adjacent tissues was examined by immunohistochemistyThe immunohistochemical expression of GRIM-1 was investigated in 33 NSCLC (17 squamous cell carcinomas; 13 adenocarcinomas and 3 Adenosquamous carcinomas) and counterpart normal tissues.2. Protein extraction and Western blot analysisTotal protein were extracted from 31 cases NSCLC and adjacent tissues, respectively, and the expression of GRIM-1 was measured by Western Blot.3. Analyze the relationship between GRIM-1 and clinical-pathologic features in lung cancerGroup GRIM-1 expressions according to sex, age, smoking, primary lesion, lymph node or distant metastasis and clinical staging of NSCLC (non-small cell lung carcinoma, NSCLC) patients, then analyze the relationship between GRIM-1 and clinical-pathologic features in NSCLC.3. Statistical methodAll experiments were performed at least three independent times. Data were expressed as the means±standard and were analyzed for significant differences by independent Student's t test and one-way ANOVA with SPSS 11.5. Differences were considered statistically significant if P value <0.05.Result1. The cellular distribution of GRIM-1 in lung cancer and adjacent tissues GRIM-1 was dominantly located in the cytoplasm of normal alveolar epithelial cells and cancer cells.2. The relationship between the expression of GRIM-1 and clinical-pathologic features in lung cancerSet 33 cases GRIM-1 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-1 protein in lung cancer tissues and clinicopathological features of patients.The positive rate of GRIM-1 was significantly higher in normal lung tissues than in lung cancer tissues(P<0.01).The positive rate of GRIM-1 has no differences among the patients'sex,age,smoking condition and histology.However,its relationship with clinic staging was established(P<0.01),and the positive rate of GRIM-1of stage I~Ⅱwere significantly higher than those of stageⅢ～IV.3. Detect GRIM-1 protein expression in 31 cases lung cancer and adjacent tissues using Western Blot analysisTotal protein was extracted from 31 cases lung cancer and adjacent tissues, respectively, and the expression of GRIM-1 protein was measured by Western Blot.ConclusionGRIM-1 was dominantly located in the cytoplasm of normal lung cells and cancer cells.The positive rate of GRIM-1 was significantly higher in normal lung tissues than in lung cancer tissues(84.85% vs.63.64%,P<0.01).GRIM-1 expression is down-regulated along the primary lesion and clinical development of lung cancer, and no correlation with lymph node or distant metastasis. GRIM-1 nuclear expression is an early and important phenomenon in the pathogenesis of lung cancer. The findings indicate that the reduction of GRIM-1 may play an important role in lung cancer carcinogenesis and offer a potential suitable target for early diagnosis.