The Correlation Of The Expression Of MGMT, NF-κB And TP53in Primary Glioblastoma With Prognosis

Background Both the morbidity and grade malignancy of Glioblastoma(GBM) were the highest in glioma. O6-methylguanine-DNA methyltransferase (MGMT) is closely related to the prognosis of patients, and the MGMT promoter methylation may in turn affect the expression of MGMT, but it is not the only factors. The research about the relationship in nuclear factor κB (NF-κB),mutant P53(TP53) literature and the regulation of MGMT gene’s expression is builted using tumor cell lines by plasmid NF-κB and TP53were observed in the regulation of expression of MGMT, there are some differences between this and the direct detection of tumor specimens. In this experiment, We used resected GBM tumor specimens to detect the NF-κB, TP53expression levels,and analysis it’s correlation in the prognosis of patients and the MGMT.Objective To research the levels of MGMT, nuclear NF-κB and TP53expressed in primary glioblastoma, and analysis the correlation with patient’s prognosis.Methods Summarize the34patients confirmed primary glioblastoma by accepted surgical resection and biopsy at Bejing Sanbo brain hospital in the period of June2008and August2011. The expression of NF-κB, TP53and MGMT were determined by immunohistochemistry. All patients using Temozolomide(TMZ) for Concurrent chemoradiotherapy after surgery and adjuvant TMZ chemotherapy alone, patients were followed up to record the progression-free survival (PFS) and overall survival (OS).Result1. The results of immunohistochemistry showed that among the34cases of primary GBM specimens,25cases were expressed MGMT, the positive expression rate is about73.5%;25cases were expressed TP53, the positive expression rate is about73.5%;24cases were expressed NF-κB, the positive expression rate is about70.6%.2. The relationship between different expression levels of MGMT, TP53, NF-κB and the patient’s prognosis:1) MGMT-negative patients with a median PFS of21months, PFS rate in6months was89%and the median OS was26months, OS rate in1year was78%, and in2year was56%; MGMT-positive patients’median PFS was8months, PFS in6month was56%, median OS was14months, OS in1year was52%, in2year was20%.2) TP53-negative patients with a median PFS of12months, PFS rate in6months was50%, the median OS was17months, OS in1year was88%, OS in2year was50%; TP53-positive patients with a median PFS of8months, PFS rate in6months was27%, median OS was13months, OS in1year was54%, OS in2year was23%.months PFS rate was27%, median OS was14months,1year OS was54%,2-year OS was23%.3) NF-κB-negative patients with a median PFS of22months, PFS rate of6months was56%, median OS was26months, OS rate in1year was89%, OS rate in2-year was67%; NF-λB positive patients with the median PFS of8months, PFS rate in6months was27%, median OS was13months, OS in1year was48%, OS in2-year was16%.3. Using the Spearman correlation analysis to compare the relationship of the different expression levels of MGMT, TP53, NF-κB in different groups of patients and the patients’ PFS, OS rate:1) MGMT negatively correlated with PFS (r=-0.563, P=0.001), MGMT showed a negative correlation with OS (r=-0.543, P=0.001);2) TP53was negatively correlated with PFS (r=-0.470, P=0.000), TP53and OS was negatively correlated (r=-0.455, P=0.000);3) NF-κB and PFS were negatively correlated (r=-0.483, P=0.00), NF-κB and OS were negatively correlated (r=-0.463, P=0.00).4The correlation between the expression of NF-κB/TP53in tumor tissues and MGMT:In34patients’tumor tissues, NF-κB-positive expression patients had a concordance rate of68%in MGMT-positive patients(17/25), there were3cases NF-KB-negative expressed patients among the9MGMT-negative expressed patients, the results suggest a positive correlation(r=0.360, P=0.036); TP53-positive expression patients accounted a concordance rate of84%in MGMT-positive expression patients(21/25), there are5cases TP53-negative expressed patients among9MGMT-negative expression patients, the results suggest a positive correlation(r=0.493, P =0.003).Conclusions1The expression levels of MGMT, NF-κB and TP53has a negative correlation with the prognosis in patients in the primary glioblastoma tissue;2There is a positive correlation between NF-κB/TP53and MGMT, and NF-κB/TP53affects the expression of MGMT;3NF-κB, TP53can be used as indicators to predict prognosis of patients with primary glioblastoma.