The Correlation Study Of EGFR Gene And PI3K/Akt/mTOR Signal Pathway In NSCLC

Background EGFR-TKI has made great progress used in the treatment ofNSCLC, and acquired favorable effects. However, the problem of durg-resistance isurgently needed to be solved at present. Preliminary studies suggest that the activationof PI3K/Akt/mTOR signaling pathways is considered to be one of the reasons forEGFR-TKI resistance at present, but the specific mechanism is still unclear. Thispathway is activated in a wide variety of tumor cells and is closely related to the tumoroccurrence and development. The correlation study of the pathway and EGFR gene innon-small cell lung cancer is not many, and the current study is mostly at the proteinlevel, research on mRNAlevel rarely reported.Objective To detect the genetic mutations situation and mRNA expression levelof PI3K/Akt/mTOR pathway and EGFR gene in untreated NSCLC patients, explore therelated mechanisms of PI3K/Akt/mTOR pathway in EGFR-TKI resistance, and lay thefoundation for the further use of PI3K pathway inhibitor in EGFR-TKI resistancepatients.Method This study involved135NSCLC patients without any treatment, and therelevant clinical data were recorded. EGFR E18, E19, E20, E21and PIK3CA E9, E20gene mutation of tumor cells were detected, using xTAG-liquid chip technology. ThemRNA expressions of PIK3CA, Akt1, mTOR and EGFR were detected, usingthe branched DNAliquid chip technology.Result EGFR gene sensitive mutation rate is48.1%, with exon19(mutation rate22.2%), and exon21(mutation rate25.2%) for most. EGFR gene drug-resistantmutation rate is0.7%. PIK3CA gene mutation rate is1.5%, and all of the mutations arelocated in exon9. High expression level of the PIK3CA gene holds the highestproportion, compared with EGFR, Akt1and mTOR gene, which revealed statisticallysignificant difference (p<0.05). EGFR gene sensitive mutation is correlated to smoking history (r=-0.232, p<0.01), pathologic types (r=-0.307, p<0.05) and the differentiationdegree (r=0.234, p<0.01). PIK3CA gene mutation is correlated to pathologic types(r=0.334, p<0.01). EGFR gene expression is correlated to pathologic type (r=-0.216,p<0.05). EGFR, Akt1and mTOR gene expressions are correlated with each other(r=0.342,0.320and0.281; p<0.01). EGFR, Akt1, mTOR gene expression are correlatedto sensitive EGFR mutation (r=0.582,0.238and0.186; p<0.05or0.01).Conclusion EGFR mutation rate rises along with the tumor differentiationdegree. EGFR, Akt1and mTOR gene are co-expressed. Patients with sensitive EGFRgene mutation reveal a higher expression of EGFR, Akt1, mTOR gene than wild type.