Clinical Pathological Significance Of K-RAS、B-RAF、PI3K And PTEN Protein Expressions In Non-small Cell Lung Cancer

Objective: Lung cancer is the common malignancy with high incidence andmortality. There are one million persons of whom the lung cancers are diagnosed in theworld each year. The non-small lung cancer (NSCLC) occupies80percent of the cancer.The surgical operation is still the most common method for treatment of the patients,but many patients need the chemotherapy because the surgery chance is lost, when thecancers diagnosed have developed into the high stage. However, chemotherapy lacks ofspecificity for the cancer and often has many side effects on patients. Recently, thepersonalized therapy, particularly molecular target therapy has been applied in NSCLCand receives much attention from oncologists. Tyrosine kinase inhibitor (TKI) is arepresent of molecular target drugs, which has succeed in treatment of the NSCLCpatients whose cancer bring epidermal growth factor receptor (EGFR) with some exonmutations. However, a lot of patients can not get benefit from TKI because of primaryand secondary drug resistances of the cancer. The reason of drug resistance is owing todownstream key molecular mutations of the EGFR signal pathways, and these mutantproteins can independently induce the cells to proliferate persistently whetherinhabitation or activation of EGFR. The main downstream signal transduction pathwaysof EGFR contain both of RAS/RAF/MEK/ERK and PI3K/AKT pathways. Theactivated mutations are usually detected in K-RAS, B-RAF or PI3K from NSCLCtissues, and these mutations become the resistance markers of the drugs. Generallyspeaking, mutations of genes would influence the expressions of their coding proteins.While, there are few reports about protein expressions of these genes and the relation ofthese protein expressions to the drug resistance of NSCLC. PTEN could suppress theactivity of PI3K/AKT signal transduction pathway, and its expression would influencethese signal proteins to express perhaps. We have also found loss of PTEN protein expression in NSCLC tissues. Therefore, the detection of K-RAS, B-RAF, PI3K andPTEN protein expressions may be helpful for us to select persons who can benefit fromTKI therapy.Methods: NSCLC tissues of119and their surrounding tissues of26from surgicaloperation were selected. Immunohistochemistry was used to detect the proteinexpressions of K-RAS, B-RAF, PI3K and PTEN of the caners and their surroundingtissues. The SPSS statistic software was used to analyze the correlation of these proteinexpressions to clinical pathological agents of the patients and the correlation amongthese protein expressions.Results: The positive rates of K-RAS protein expression in NSCLC and theirsurrounding tissues were40.3%and42.3%respectively, there was no statisticsignificance (P>0.05), but the expression of K-RAS protein in NSCLC tissues wassignificantly related to that of their surrounding tissues (r=0.456, P<0.05) in the samecases. In NSCLC group, the K-RAS protein expression had no significant relation to sex,age, smoking history of the patients and lymph node metastasis, histological type,differentiation of the cancers (P>0.05).The positive rates of B-RAF protein expression in NSCLC and their surroundingtissues were26.1%and26.9%respectively, there was no statistic significance (P>0.05),and the expression of B-RAF protein in NSCLC tissues also had no significant relationto that of their surrounding tissues (r=0.079, P>0.05) in the same cases. In NSCLCgroup, the positive rates of B-RAF protein expression in groups of smoking andnon-smoking patients were12.2%and33.3%respectively, there was significantdifference (P<0.05); those in groups with and without lymph node metastasis were12.9%and40.4%respectively, there was significant difference (P<0.05); in squamouscell carcinoma, the positive rates of B-RAF protein expression in groups of high-middledifferentiation and low differentiation were10.5%and42.9%respectively, there wassignificant difference(P<0.05), but the expression had no significant relation to sex andage of the patients (P>0.05).The positive rates of PI3K protein expression in NSCLC and their surroundingtissues were39.5%and7.7%respectively, there was significant difference (P<0.05),but the expression of PI3K protein in NSCLC tissues had no significant relation to thatof their surrounding tissues (r=0.365, P>0.05) in the same cases. In NSCLC group, thepositive rates of PI3K protein expression in groups of adenocarcinoma and squamouscell carcinoma were33.3%and54.5%respectively, there was significant difference (P<0.05). But, the PI3K protein expression had no significant relation to sex, age,smoking history of the patients and lymph node metastasis, differentiation of thecancers (P>0.05).The positive rates of PTEN protein expression in NSCLC and their surroundingtissues were54.6%and65.4%respectively, there was no statistic significance (P>0.05),but the expression of PTEN protein in NSCLC tissues was significantly related to thatof their surrounding tissues (r=0.566, P<0.05) in the same cases. In NSCLC group, thePTEN protein expression had no significant relation to sex, age, smoking history of thepatients and lymph node metastasis, pathological type, differentiation of the cancers(P>0.05).In NSCLC tissues, the expression of K-RAS protein had no significant correlationto that of B-RAF (r=-0.200, P>0.05), but the expression of K-RAS protein hadsignificant correlation to that of PI3K (r=0.212, P<0.05). The expression of PI3Kprotein had no significant correlation to that of PTEN (r=0.115, P>0.05), and theexpression had no correlation to that of B-RAF (r=-0.010, P>0.05).Conclusion:1The NSCLC with K-RAS protein expression in their surrounding tissues wouldalso express the protein;2The NSCLC of poorly differentiated squamous cell carcinoma in non-smokingpatients without lymph node metastasis would be likely to express B-RAF protein;3The squamous cell carcinoma of NSCLC would be likely to express PI3Kprotein;4The NSCLC without PTEN protein expression in their surrounding tissueswould not express the protein;5The NSCLC with K-RAS protein expression would also express PI3K protein;6Detection of K-RAS, B-RAF, PI3K and PTEN protein expressions may behelpful for us to screen persons who could benefit from TKI therapy.