Study Of Pi3K/Akt/mTOR Signal Transduction Pathway Related Proteins And Gene Genetics Of Glioma

Objective: To investigate the expression of protein-PI3K, mTOR and PTEN thatcorrelated with PI3K/AKT/mTOR signaling pathway in human gliomas and the clinicalsignificance. To investigate the correlation between loss of heterozygosity (LOH) onchromosome10q and pathological features, development, prognosis of different gradeglioma. Methods: Envision Immunohistochemistry technique was applied to detect theexpression of PI3K, mTOR and PTEN in75formalin-fixed paraffin embedded samples ofgliomas(glioma group) and10cases of normal brain tissue(normal control group), LOH10q was detected by interphase fluorescence in-situ hibridization (FISH) in75cases ofglioma. Results:75cases of gliomas’ PI3K protein positive expression rate was56.0%(42/75), mTOR protein expression positive rate was78.7%(59/75), PTEN protein positiveexpression rate was38.7%(29/75).10cases in control group PI3K, mTOR, PTEN proteinpositive expression rate were10.0%(1/10),10.0%(1/10),100.0%(10/10) respectively.Glioma group of PI3K, mTOR protein positive expression rate were significantly higherthan control group (all P＜0.05), and the PTEN protein positive expression rate below thecontrol group significantly (P＜0.05).30cases of grade Ⅱ gliomas’ PI3K protein positiveexpression rate was20.0%(6/30), mTOR protein positive expression rate was63.3%(19/30), PTEN protein positive expression rate was53.3%(16/30);45cases of grade Ⅳglioblastomas’ PI3K, mTOR, PTEN protein positive expression rate were80.0%(36/45),88.9%(40/45),28.9%(13/45) respectively. Grade Ⅱ gliomas’ PI3K, mTOR protein weresignificantly lower than grade Ⅳ glioblastomas (all P＜0.05), PTEN protein wassignificantly higher than grade Ⅳ glioblastomas (P＜0.05). Gliomas of different grade ofPI3K, mTOR, PTEN protein positive rate in age, sex, tumor location, nations were notstatistically different (P＞0.05). There were no correlation between PTEN and PI3K,mTOR protein (r=0.068, P=0.560; r=0.012, P=0.915). PI3K and mTOR protein expression was positively correlated (r=0.456, P=0.000).75cases of gliomas,18cases(24.0%) showed no chromosome10q LOH,39cases (52.0%) showed chromosome10qLOH,18cases (24%) showed chromosome10polysomy. There were difference betweenage, grade when10q LOH contred with no10q LOH (P＜0.05) and there were nostatistically difference between different age and tumor location (P＞0.05). Survivalanalysis showed that the pathological grade, PI3K protein expression, chromosome10qLOH can influence glioma patient survival time. Conclusions: PI3K/Akt/mTOR signaltransduction pathway is over-activated in gliomas, which is closely correlated to thegrade-malignancy. The pathological grade, PI3K protein expression and chromosome10qLOH are prognostic factors in patients with glioma.