The Clinical Study Of Five Serum Tumor Markers In Lung Carcinoma

Objection:1 To study the adjuvant diagnosis value of the 5 serum tumor markers (TM) of tissue polypeptide specific antigen (TPS) , neuron-specific enolase(NSE) , carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA199) and cytokeratin fragment 19 (CYFRA21-1) in lung carcinoma, include the relationship between the serum level of the TM and the gender , age and pathology respectively ,the relationship between the markers themselves and the value of combined detection of the 5 tumor markers.2 To study the discrimination value of the tumor markers to the pathology, affirm the cut-off value.3 To study the serum level of the 5 tumor markers related to the clinical stages and try to quantitatively analyze the diagnosis value of the serum level of the tumor markers to the clinical stages division.4 To study the value of 5 tumor markers in the medical therapy of LC, include the observation of the tumor markers and the effect evaluation by the tumor markers.Method:The in-patients with lung carcinoma in NanFang Hospital of The Southern Medical University were included through 2003 to 2004 according to the different standard of each part of the study. The serum level of TPS, NSE, CEA, CYFRA21-1and CA199 were examined. The clinical reference of the patients such as gender, age, KPS, pathology, clinical stage and effect were summarized and grouped. All the deta was analyzed using the statistic software package SPSS 10.0.Result:1 The adjuvant diagnosis value of the 5 tumor markers1.1 The correlation of the serum level between the TM and gender or ageThe 92 patients were grouped according to the gender, there were no significant difference between the two groups. The patients were divided into 3 groups by age: group I (=70, n=17), group II (50-70, n=45), group III (=50, n=30), there were no significant difference between the three groups of the serum level of each tumor marker.1.2 The correlation of TPS between CA19-9, NSE, CEA and CYFRA21-1The result showed that there exited positive correlation between the serum levelof TPS and CEA, CYFRA21-1, NSE with the rs of 0.335 (P<0.05), 0.574(P<0.00),0.255(P <0.05) respectively, and a negative correlation between TPS and CA199( r s= 0.164, P>0.05).1.3 The serum level of the 5 tumor markers in the groups of lung carcinoma and controlThe serum level of the 5 tumor markers of the group lung carcinoma increased significantly compared with that of the groups of benign lung disease(BLD) and health controKP <0.001 ),there was no statistic difference between the groups of BLD and health control of the TM repectively(P>0.05 )1.4 The positive rate of each TM in the groups of lung carcinoma and controlThe positive rate of each TM differed significantly between the groups of LC, BLD and health control (P<0.05).The positive rate of 5 TM in LC were significantly different (P=0.000) with TPS, NSE, CEA a relatively higher positive raterespectively, the positive rate of CA199 was low (23.75%).Compared with the control of BLD, the sensitivity and specificity of TPS were 66.40%, 87.50% respectively with the cut-off value of 140U/L, the sensitivity and specificity of TPS were 52.20%, 93.70% respectively with the cut-off value of 168.75U/L.1.5 The combined detection of TMCompared with the BLD, the sensitivity, specificity, effectiveness of TPS were 81.11%n 86.36%> 82.84%, the sensitivity is relatively higher than the others(P<0.05) and with a lower specificity, the effectiveness is high, the sensitivity and effectiveness of CA199 were 23.75%, 35.42%, the sensitivity is low. CEA and CYFRA21-1 both had a higher specificity of 100.00%. The combinations' sensitivity were increased with the number of TM increased, but the specificity went down, in which the combinations included TPS is more sensitive, the combinations included TPS were relatively higher with sensitivity.1.6 The diagnosis value of the 5 TM in different pathology type of LCCompared in the three groups of lung carcinoma: squamous cell carcinoma, adenocarcinoma and small cell carcinoma, only NSE differed significantly(P=0.000), the positive rate in SCLC is the relatively higher(87.5%); the positive rate of each TM differed significantly in each group of pathology; the positive rate of TPS in the three groups reached 75.00%, 87.50%, 84.00%, CEA in adenocarcinoma and CYFRA21-1 in squamous cell carcinoma also have a relative higher positive rate which was 65.62%, 52.38% respectively.1.7 The serum level of 5 TM in different pathology of LCCompared in the three groups of lung carcinoma, only the serum level of NSE differed significantly (P <0.001) , it was also the highest in SCLC. 2 The value of TM to differentiate the tissue type of LC2.1 The positive rate, serum level and distribution of NSE in SCLC and NSCLC patientsThe positive rate in the patients of SCLC (76.90%) was significantly higher than that of the NSCLC(35.80%)( P<0.001). Serum NSE level in SCLC patients was significantly higher than that in NSCLC patients (P<0.0001).In NSCLC patients, the 50, 75, 85, 95 percentile serum NSE levels were 10.2, 15.8, 38.2 and 63.6 fxg/L, respectively, the 50, 75, 85, 95 percentile serum NSE levels in SCLC were 23.10> 48.8 and 132.2/^g /L, respectively.2.2 The characteristic of the cut-off value of NSE under the Receiver operating characteristic(ROC) curveROC curve showed the area under the curve was 0.711(P <0.00). With the cut-off level of 15.45/^ /L, the sensitivity and specificity were 66.7%, 65.7% respectively, when the cut-off value was 63.6/ig/L, the specificity was 95.1%.2.3 The value of CEA to distinguish the adenocarcinoma LCThere was no significant difference of positive rate of CEA between adenocarcinoma (60.98% ) and non-adenocarcinoma (48.65%) patients (F>0.05), ROC curve showed the area under the curve was 0.0959(jP=0.151), that showed there was no value of CEA to distinguish adenocarcinoma from non-adenocarcinoma in LC patients.3 The relationship between the clinical stages and the serum level of the 5 TM 3.1 The positive rate of TM in the different TNM stages of LCThe result showed that the positive rate of TPS, CEA went up with the stages, there were significant difference between the stage I/II and stage III, stage HI and stage IV(F<0.05). The positive rate of CYFRA21-1 and CA199 showed no significant difference between the clinical stages(P>0.05). The positive rate of NSE showed significant difference between the stages(P<0.05), the positive rate in stageIV was relative higher, but the the positive rate of NSE in stage I/II and III were 37.50%, 23.33% respectively(P<0.05). The positive rate of 5 TM showed significant difference in the stage I/II (P<0.05).3.2 The serum level of TM in the different stages of LCThe result showed that the serum level of NSE, TPS, CEA went up with the stages, there were significant difference between the stage I/II and stage IV, stage III and stage IV(P<0.05). The median value of serum level CYFRA21-1 and CA199 had the tendency of going up with the stages, but there existed no significant difference(P>0.05).3.3 The relationship between 5 TM and T, N, M and KPSThe result showed only TPS differed among the different T grades (P<0.05), so CYFRA21-1 among the different N grades(P<0.037). The level of NSE, TPS, CEA in the Mi were significantly higher than the Mo. The test of Spearman showed that TPS was negative related to KPS(P<0.05).3.4 The combined detection of TM to stage IV of LCThe ROC showed that the serum of TPS, CEA, NSE had the value of diagnose stage IV(p=0.039, 0.003, 0.019, respectively), with the specificity at least 95%, the cut-off value of the 3 TM were 839.20U/L, 37.20ng/ml, 62.75 n g/L respectively, the sensitivity and specificity of the three-combined detection were 61.2%, 84.4% respectively.4 The observation of 5 TM in the treatment of LC 4.1 The relationship of the change of the serum level of the TM and effectThe result showed that the level of CYFRA21-1 and TPS decreased significantly after the chemotherapy in the TR(response ) patients (P<0.05) and increased in the PD(progressive disease) patients significantly(P<0.05), there was no significantly changing in the SD (stable disease) patients. NSE decreased significantly in the TRpatients(P<0.05), with no significant change in the SD and PD patients(P>O.O5), the level of CEA increased significantly in the PD patients (P<0.05) . there was no significant change of CA199 in the three groups of patients after the treatment respectively(i>>0.05).4.2 The relationship between the serum level of TM before the chemotherapy and the effectThe result showed that among the three groups patients of different effect there were no significant difference of serum level of each TM before chemotherapy (P>0.20 respectively).4.3 Concordance between clinical and TM evaluation of response of the treatment to LC patientsThe result showed that there was no significant difference among the total concordance rate (OR+SD +PD)of the 5 TM, but the concordance rates in both TR and PD were different significantly(P<0.05), the concordance rates of TPS and CEA were relative higher while CA199 had a low concordance rate.4.4 The evaluation of effect with different grades of TMEvaluating the effect with different grades of pro-treatment TM , it showed there exited significant difference among the total concordance rate (OR+SD +PD)and the TR+PD of the different grades of TM respectively (i><0.05, P<0.000), with the tendency of the concordance going up with the upgrade of the TM.4.5 The changing of the TM after treatment with IressaThe result showed that the serum level of TPS decreased significantly in the TR patients (/><0.05) , increased significantly in the PD patients (P<0.05) and had no difference in the SD patients (P>0.05) . The serum level of CEA, NSE, CA199 and CYFRA21-1 had no significant changing after the treatment at any group (i>>0.05 respectively) .4.6 The relationship between the serum level of TM before the treatment with Iressa and the effectThe result showed that there was significant difference of the serum level of TPS before the treatment among the three groups patients (P<0.05), but there was no linear relationship between the effect and the pro-treatment serum level, there was no significant difference of the other TM before the treatment respectively (P<0.05).Conculsion:1 These 5 tumor markers have different clinical application of adjuvant diagnosis value of LC .The combined detection can vate the value of clinical application.2 Serum NSE level can help distinguish SCLC and NSCLC, which is simple and cost-effective.3 The serum level of TPS, CEA, NSE increase in the advanced clinical TNM stage, and can be used to the diagnosis of stage IV lung carcinoma, the three-combined detection can elevate the clinical value and be applied in the clinical.4 The changing after the chemotherapy of the 5 TM partly reflect the therapic effect, there are no statistic relationship between the serum level of the 5 TM before the treatment and the clinical effect, the relatively higher level TM before the treatment have a better concordance with the object clinical assessment , the TM monitering should choose the relatively higher one before the treatment.5 Monitoring serum TPS level can help evaluate the therapic effect of Iressa in advanced lung adenocarcinoma patients, which is simple and cost-effective. The serum level of TPS before therapy can not prognosticate the effect of the treatment with Iressa,...