The Protein Expression Of GRP94/78and Correlation Factors In NSCLC And Its Signifinance

Purpose: To investigate the relationships between the expression of glucose-regulatedprotein94and78(GRP94, GRP78), EGFR,IGF1R and their downstream signaling factorsEGR1, Akt,p-Akt,Erk,p-Erk in human NSCLC;and the correlations with clinical data.Object: Lung cancer tissues and paracancer normal lung tissues, were collected from109patients undergoing surgical resections of lung cancer at the Anhui Provincal hospital andthe first hospital of JiLin University. The Samples include55SCC pathological sections,35ACC pathological sections,10SCC frozen samples and9ACC frozen samples.Methods: Telephone following up regarding on life span and postoperative treatmentwas carried out with90patients who visited at Anhui Provincal hospital. Immunohisto-chemisty was used on90NSCLC pathological sections to detect the expression of GRP94andGRP78. Western Blotting was employed for detection of the expression of ER stress factors,GRP94and GRP78, and signaling pathways of EGFR、IGF1R、EGR1、AKT and ERK1/2on19fresh frozen samples which were pathologically diagnosed as NSCLC.Results:1.pathology diagosis of cell differentiations may influence the survival rate onpulmonary adenocarcinoma;tumor T/N staging and WHO clinical stage are the most factorsclosely correlated with the survival rate in both lung squamous cell carcinoma andadenocarcinoma.2.There were significant overexpressions of GRP94and GRP78at protein levels in lungcancer tissues as compared to adjuncent normal tissues in NSCLC;the difference for GRP94and GRP78protein expression between cancer tissues and paracancer tissues wassignificant.The protein expression of GRP94and GRP78correlated with pathologydifferentiation,tumor T staging,tumor N staging,WHO clinical staging.3.The overexpression of GRP94and GRP78in NSCLC correlated with life span andsurvival rate, which showed that the higher expression of GRP94/78, the poorer survivalrate,which suggested that cell ER stress factors GRP94and GRP78can be used as anindicator for prediction of prognosis.4. EGFR、IGF1R、EGR1、Erk1/2and Akt proteins were overexpressed in more than30% of tested cancer tissues，which suggested above lung cancer correlators act some roles inNSCLC;p-Erk and p-Akt proteins were overexpressed in more than50%of tested paracancertissues, which suggested they involed in neoplasm invasiveness.5.The difference for EGFR、IGF1R、EGR1、p-Erk、p-Akt protein expression betweencancer tissues and paracancer tissues were significant in NSCLC,and there were relationshipsamong the protein expression of EGFR、IGF1R、EGR1、Erk1/2、p-Erk、Akt、p-Akt.6.In NSCLC,the protein expression of EGFR、IGF1R、EGR1、Erk1/2、Akt、p-Erk、p-Akt correlated with pathology type, pathology differentiation, TNM clinical staging,tumorN staging,tumor T staging,smoking history,Ki67expression.7. In squamous carcinoma,33%of samples overexpressed EGR1and that was correlatedwith the overexpression of EGFR. However, in adenocarcinoma, the expression of EGR1wasdecreased in44%of the sample with EGFR/IGF1R-overexpressed tissues. The above dataimplicated that, the expression of EGFR、IGF1R and EGR1are clearly correlated with thedevelopment and progress of NSCLC. More interestingly, EGR1may play different role insquamous cell carcinoma and adenocarcinoma NSCLC.Conclusions: GRP94and GRP78might be a potential indicator for survival of NSCLC.The expression level of GRP94may can be served as an additional markers for identifying thegrade of differentiation, while GRP78may be used for indicating the clinical stage ondiagonosis of NSCLC. The activating status of EGFR、IGF1R are clearly correlated with thedevelopment and progress of NSCLC, and EGR1may plays a different role in squamous cellcarcinoma and adenocarcinoma.