| Glioblastoma is the most common and highest degree of malignant of the intracranial tumors, accounting for 15% of all intracranial tumors, accounted for 50% of glioma(including astrocytoma, glioblastoma, oligodendroglioma, ependymoma and of unknown origin or mixed origin of glioma). Glioblastoma patients generally have a poor prognosis and short survival: surgical resection of the tumor with radiotherapy, anti-tumor drug in the treatment of conditions, median survival was only 14.6 months with the disease, and the median progression free survival was only 6.9 months. One of the important reasons for the poor prognosis and short survival period is that the tumor is not sensitive to the chemotherapy drugs, which especially is temozolomide(TMZ).With the development of molecular biology for glioblastoma, malignant tumor drug resistance mechanism and drug resistance related genes and proteins constantly in-depth, repair genes associated with malignant tumor drug resistance becomes more and more clear. In recent years, it is found that repair of the h MSH6 gene is one of the main members of the DNA mismatch repair gene system, the role is in cell replication or transcription of specific recognition mis-matched paired bases, and remove and repair, to ensure that the DNA replication, high fidelity to maintain base for stability and play an important role in the mechanism of the malignant tumor drug against the chemotherapy drugs. At present, the research on the expression of repair genes in the clinical, especially the prognosis of malignant tumors is gradually popular. The discovery of repair gene h MSH6 and its protein expression provides a new way to predict the clinical prognosis and the development of anti tumor drugs in the future.Objective: To study the surgical removal of the tumor specimens from 30 patients with pathologically proved primary glioblastoma(WHO grade IV) by retrospective analysis. Immunohistochemistry staining detection method to repair the h MSH6 gene in primary glioblastoma patients with tumor samples were sectioned in the expression, combined with the essential condition of patients and clinical data, after screening and verification to find the impact of primary glioblastoma patients survival and prognosis related factors. To investigate the glioblastoma diagnosis, treatment methods and mismatch repair gene h MSH6 and primary prognosis of glioblastoma survival correlation analysis, primary glioblastoma patients with clinical severity and prognosis and provide a theoretical principle and may provide new ideas for the future treatment of glioblastoma, anti glioblastoma chemotherapy drug development.Method: 1, this study collected through the system of medical records and telephone follow-up for 30 cases of primary glioblastoma patients with complete basic data and clinical data(age, gender, number of hospitalized, hometown, home address, telephone number, preoperative KPS score, and surgical resection condition, edema grade, postoperative survival time) and the tumor pathology. 2, immunohistochemical staining method(two step method) to detect the expression of h MSH6 in glioblastoma pathological specimens, and record images pathological photos. 3, Analysis data by using application of SPSS 17.0 statistical software processing, using Pearson’s chi square test analysis of h MSH6 between high expression group and low expression of groups of patients with clinical basic characteristics(age, gender, preoperative KPS score, operation excision, edema grade, postoperative survival time); using Cox regression proportional hazards model respectively for univariate and multivariate analysis screened the independent variables affect the prognosis of glioblastoma multiforme(GBM); using the Kaplan Meier method and the log rank test analysis, comparative independent variables under the condition of the difference in survival time and draw the Kaplan Meier survival curves.(the above calculation results of hypothesis test, when P is less than 0.05 considered statistically significance)Results:(1) 30 cases of glioblastoma patients, 18 males and 12 females. The sex ratio was 1.5:1. The age ranged from 25 to 83 years old, average 55.4 years old, the median age was 58 years. The preoperative KPS score of 60 to 90, median preoperative KPS score of 80. Surgical methods: 20 cases of glioblastoma patients with total excision, 9 cases with subtotal resection, 1 cases with partial resection. The survival time of 3 ~ 38 months, average 15.1 months, the median survival time was 13 months.(2) 30 cases of glioblastoma specimens, h MSH6 positive expression rate was 86.7% totally. The h MSH6 high expression group a total of 16 cases, accounting for 53.3%. h MSH6 low expression group a total of 14 cases, accounting for 46.7%.(3) a Pearson chi square test(Pearson Chi Square) glial blastoma in pathological specimens h MSH6 expression level between the two groups in gender(P =0.052), age(P =0.732), KPS score before operation(P =0.440), surgical excision(P =0.901), MRI brain edema(P =0.161) don’t have statistical significance(P value is more than 0.05).(4) Cox proportional hazards regression model analysis of univariate and multivariate results suggest that the expression of h MSH6 and KPS score before operation is the independent variables influence the postoperative survival time(P value is less than 0.05).(5) survival analysis of Kaplan Meier method and log rank test h MSH6 in glioblastoma cells expression quantity is high, patients postoperative survival time is short and the difference has statistical significance(log rank test, P = 0.0001, X 2=10.685); preoperative KPS score higher(more than or equal to 80), patients with postoperative survival time longer, and the difference has statistical significance(log rank test, P = 0.0001, X 2=11.554).Conclusion: the expression level of h MSH6 in the glioblastoma tissue was high, the overall positive expression rate was 86.7%. The expression level of h MSH6 in patients with glioblastoma, and preoperative KPS score were independent influencing factors of prognosis. The expression level of h MSH6 in patients with glioblastoma was related to survival time of the patients, the higher expression level, the shorter survival time of the patients. The expression level of h MSH6 can provide a new feasible solution for the prognosis of glioblastoma. The preoperative KPS score and survival time is related to KPS, the higher score(≥80 points), the longer survival time will be. |
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