| Objective:Human glioma, the most common intracranial malignant tumor, occurred in neuroderm, is difficult to radically resect. Even if supplemented by postoperation chemotherapy or radiotherapy, prognosis of patients is still very poor. Target therapy is one of the most important treatment to malignant tumors in recent years. Analyzing related cell signaling pathways and genes associated with the glioma and looking for effective therapeutic targets, become a hotspot in the research of glioma therapy. By detecting the expression of cell cycle protein Dl (CyclinDl) and P16 gene in glioma and exploring their correlation and significance with clinical characteristics of human glioma, this study provided the reference for judging the prognosis of patients with glioma and datas for seeking new therapeutic targets.Methods:Human glioma specimens from 65 patients who underwent surgery from December 2011—February 2013 at the Department of Neurosurgery, the First Affiliated Hospital of Dalian Medical University. There was no brain metastatic tumor and malignant tumor in other organs of the patients. And they had no history of preoperative radiotherapy, chemotherapy and other anti-tumor treatment. We collected complete clinical and pathological informations of all patients. By following up of the 65 patients (follow-up date until February 1,2015), we recorded 39 death cases and 26 survival cases. Complete data were obtained from dead cases and censored data were obtained from the postoperative death or death of non-primary disease. MaxVision TM method was used to detect the expression of CyclinDl and P16 in 65 glioma specimens. SPSS 17.0 statistical software was used for statistical analysis, and the chi-square test was used to analyse the differences and relationship between each group(P-value less than 0.05 were considered significant). Independent risk factors affecting the prognosis of patients with glioma was measured by COX regression model(P-value less than 0.05 were considered significant). Correlation of CyclinD1 and P16 Expression were measured by Spearmen correlation analysis (P-value less than 0.01 were considered significant). Survival curves of different patient groups according to the protein expression level were drawed using the Kaplan Meier method.Results:1. Expression of P16 mainly occured in the nucleus and cytoplasm of glioma tumor. In Ⅱ, Ⅲ, Ⅳ grade, the positive expression rate were 64.29%,37.50% and 14.81% respectively. P16-positive rate in patients with low-grade gliomas was significantly higher than that in patients with high-grade glioma, P16 expression in glioma tissues showed a downward trend with increased pathological level. The difference were statistically significant (P<0.05). The expression levels of P16 had no significant relevance with patients’ gender,age,tumor size and micro-vascular density (MVD) in gliomas(P>0.05).2. Expression of CyclinD1 mainly occured in the nucleus of glioma tumor. In Ⅱ, Ⅲ, Ⅳ grade of glioma, the positive expression rate were 21.43%,41.67% and 81.48% respectively. CyclinDl-positive rate in patients with low-grade glioma was significantly lower than that in patients with high-grade glioma. CyclinD1 expression in glioma tissues showed a upward trend with increased pathological level. The difference were statistically significant (P＜0.05). The expression levels of CyclinDl have no significant relevance with patients’ gender,age,tumor size and micro-vascular density (MVD) in gliomas(P>0.05).3. In Ⅱ, Ⅲ, Ⅳ grade of the 65 glioma patients, the 2-year survival rate were 85.71%,41.67%,14.81% respectively. The difference between each groups were statistically significant (P<0.05). The 2-year survival rate of patients with high and low P16 expression were 23.26%,72.73% respectively. The difference were statistically significant (P<0.05). The 2-year survival rate of patients with high and low expression of CyclinD1 were 66.67%,17.14% respectively. The difference were statistically significant (P＜0.05).4. When a multivariate Cox proportional hazard model was constructed, histological grade, P16 and CyclinDl expression was found to have independent correlation with Patient survival (P< 0.05). Poor histological grade, Low expression of P16 and High expression of CyclinDl was significantly associated with poor overall survival.5. Correlation of CyclinD1 and P16 expression were measured by Spearmen correlation analysis, negative correlation was found in 65 glioma specimens (R=-0.381, P＜0.01)Conclusion:1. Lower expression level of P16 was detected in patient’s specimens with poor histological grade in this study, indicating that P16 may play an important role in regulating the proliferation and differentiation of glioma.2. Higher expression level of CyclinD1 was detected in patient’s specimens with poor histological grade in this study, indicating that CyclinDl may also play an important role in regulating the proliferation and differentiation of glioma.3. In this study, P16 and CyclinDl was found to be independent predictors of brain glioma patient’s survival. Kaplan—Meier survival curves also indicated that loss of P16 expression and overexpression of CyclinDl were significantly associated with poor overall survival. Thus, P16 and CyclinDl expression level may be novel prognostic factors for human brain glioma.4. Expression level of P16 and CyclinDl showed a negative correlation in 65 glioma specimens. Indicationg that Loss of P16 expression and overexpression of CyclinD1 is likely to have synergy in the occurrence and development of human brain glioma. |
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