Thymidylate Synthetase Expression In Pleural Effusion And Blood In Lung Adenocarcinoma And Its Relationship With The Effect Of Pemetrexed

BackgroundLung cancer remains the leading cause of cancer-related death worldwide. Non–small celllung carcinoma (NSCLC) accounts for80%-85%of all lung cancer cases. The majority ofthese patients already have advanced or metastatic symptoms at the time of diagnosis andchemotherapy remains the most effective treatment option to prolong survival and improvethe quality of life. Platinum-based doublet combination chemotherapy is regarded as thestandard first-line treatment for advanced NSCLC that usually consists of a platinumcompound with a third generation agent (paclitaxel, docetaxel, pemetrexed, or vinorebine).Pemetrexed is extensively used in the treatment of NSCLC. This agent is usually given incombination with platinum as the standard doublets regimen in first line chemotherapy foradvanced NSCLC. Pemetrexed, as a multitargeted antifolate cytotoxic chemotherapy agent,inhibits at least three keyt enzymes in the folate pathway (thymidylate synthase, dihydrofolatereductase and glycinamide ribonucleotide formyl transferase).It plays important roles instandard first-line, second-line and maintenance treatment for advanced NSCLC. Thymidylatesynthetase (TYMS) is the key enzyme of DNA synthesis and is one of the main targets ofpemetrexed. Study of TYMS expression level in malignant pleural effusion and blood for advanced lung adenocarcinoma patients, is helpful to guide individualized medication and toprovide a basis for clinical pleural effusion and blood specimens to replace each other assimple and effective ways to detect.MethodsWe selected58cases Stage Ⅳ lung adenocarcinoma with malignant pleural effusion whoaccept pemetrexed chemotherapy and respectively collected pleural effusion and peripheralblood. TYMS protein concentration were determined in pleural effusion and peripheral bloodsamples with double antibody sandwich ELISA method. We followed up the patients withlung adenocarcinoma, appling with RECIST1.1solid tumor curative effect evaluationstandard to observe the short-term effects.We retrospectively analyzed the relationshipbetween TYMS expression level and pemetrexed effect.At last, we observed the relationshipbetween TYMS expression level in pleural effusion and that in peripheral blood.All the data was statistically analyzed by SPSS17.0，T test was applied to analyze TYMSprotein expression and gender, age, tumor size and smoking index, etc. with Pearson linearcorrelation method was utilized to analyze the correlation between TYMS protein expressionin pleural effusion and peripheral blood serum and curative effect.Results1. There is no correlation between TYMS expression level and patient’s gender, age, tumorsize, smoking status, PS score (P>0.05).2. In all the58patients，there were27cases (CR2cases, PR25cases) in effective group and31cases (SD15cases, PD16cases) in invalid group. TYMS protein expression of peripheralblood in effective group was lower than that in invalid group, P=0.033.3. There exists significant negative linear correlation between TYMS expression in serum andPFS，r=-0.455，P＜0.01. There exists significant negative linear correlation between TYMSexpression in pleural effusion and PFS，r=-0.270，P=0.041＜0.05。4. There exists positive linear correlation between TYMS expression in pleural effusion and that in serum, r=0.348，P=0.007.Conclusions1. TYMS expression in peripheral blood may be of certain value to forecast treatmentresponse of pemetrexed for advanced lung adenocarcinoma patients. So we speculated TYMSas a predictor for pemetrexed sensitivity in therapy of NSCLC.2. Pleural effusion and blood can replace each other as simple effective predictors forpemetrexed sensitivity in the patients with advanced lung adenocarcinoma.