Objective: To explore the application value of tumor markers carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen CA724(CA724) and carbohydrate antigen CA 199(CA 199) in the diagnosis of gastric and colon tumors. Methods: Electrochemiluminescence immunoassay was used to detect 106 cases of gastric and colon tumors. The serum CEA, AFP, CA724 and CA 199 levels in patients with benign gastrointestinal diseases and 92 normal controls were analyzed by ROC curve analysis and stepwise logistic regression analysis, and the area under ROC curve (AUC) was obtained. The sensitivity, specificity, Youden index and positive likelihood ratio/negative likelihood ratio of TM were compared and analyzed. Results: TM content in gastric colon cancer group was significantly higher than that in gastric colon benign disease group and normal control group. The combined application of CA 199 has the highest sensitivity, Youden index and positive likelihood ratio/negative likelihood ratio. Conclusion: ROC analysis based on logistic regression can improve the accuracy of diagnosis. The combined analysis of CA724, CEA and CA 199 is a good combination in the differential diagnosis of gastric and colon tumors.
Carcinoembryonic antigen; Alpha fetoprotein; Carbohydrate antigen CA724 carbohydrate antigen; ca 199； Gastric neoplasms; Colon tumor
Introduction to 0
In recent years, more and more tumor markers have shown application value in screening and auxiliary diagnosis of gastrointestinal tumors. However, how to make rational use of TM to achieve the best results is still an urgent problem in clinical diagnosis. We analyzed the distribution of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen CA724(CA724) and carbohydrate antigen CA 199(CA 199) in gastric and colon tumors, and applied ROC curve [65438+.
1 objects and methods
1. 1 object
We collected 106 cases (male 6 1, female 45) with an average age of 47.3 (3 1 ~ 88), including 47 cases of gastric cancer (male 29, female 18) with an average age of 48.1. Poorly differentiated type 1 1 case; Moderate differentiation in 27 cases; 9 cases were well differentiated; 59 cases of colon cancer (32 males and 27 females), with an average age of 45.6 (3 1 ~ 88) years; Dukes in stage A, B, C and D were 9 16 and 23 1 1 case respectively. All cases were diagnosed by endoscopy, surgery and pathological examination. In addition, the average age of11(male 82) was 44.2 (2 1 ~ 72) years, including 58 cases of peptic ulcer and 53 cases of ulcerative colitis. The normal control group was 92 years old (male 55, female 37), with an average age of 45.7 (16 ~ 83). All physical examination indicators are normal, liver and kidney functions are normal, and there is no heart disease or lung disease.
1.2 method
Before surgery or radiotherapy and chemotherapy, 4 mL of fasting venous blood was taken from the patient. After coagulation, the supernatant was centrifuged at 3000 r/min for 5 min, and serum AFP, CEA, CA724 and CA 199 were detected by electrochemiluminescence immunoassay. The normal reference value is
Statistical treatment: KS normality test was performed on the concentration distribution of TM in each group, and the median and percentile (P25 and P75) of TM concentration were calculated, and KruskalWallis and MannWhitney U tests were performed. ROC curve was drawn by SPSS 13.0, and the differential diagnostic value of TM single and combined detection for gastric and colon tumors was analyzed by stepwise Logistic regression.
Two results
2. 1TM normality test The statistical distribution of four TM in each group is tested by KolmogorovSminov test, z = 1.39 ~ 4.58, P < 0.05, which belongs to non-normal distribution, and the following statistical processing adopts nonparametric test.
2.2 Except AFP, there was no statistical difference among the three groups (χ 2 = 1.759, P = 0. 184), while the TM concentration of the other three groups was statistically significant (χ 2 = 39.363 ~ 80.564, P = 0.000 ~ 0.0065438+).
According to the reference value, the positive rate of 2.3TM in each group was statistically different from that in the normal control group (P < 0.0 1, Table 2). Table 2 Positive numbers and positive rates of 2CEA, AFP, CA724 and CA 199 in each group [n (omitted)]
2.4 Logistic regression and ROC curve of gastric colon cancer group and gastric colon benign disease group.
2.4. 1 The areas under the ROC curve of serum CEA, AFP, CA724 and CA 199 in patients with gastrointestinal malignant tumor and benign disease were CEA: 0.760 (95% confidence interval: 0.695~0.826, P <
2.4.2 Stepwise Logistic regression method and ROC curve of simulated variables The Logistic regression equations of serum AFP, CEA, CA724 and CA 199 were calculated by stepwise regression with software, and AFP(P & gt；; 0. 1, where p represents the probability of gastric and colon malignant tumors based on CEA, CA724 and CA 199). p = ex/ex+ 1； x =-4.593+0.393×ln CEA+0. 1.7 1×lnca 724+0.054×lnca 199。 The model was established by stepwise Logistic regression. The ROC curve is fitted by the probability value (PRE) in the model (Figure 1). AUC of single TM and stepwise logistic regression curve combined with three TM prediction probabilities are shown in Table 3. When detecting four kinds of TM, the AUC of CEA is the largest, followed by CA724, and AFP is the smallest. However, the AUC of stepwise Logistic regression model (excluding AFP) combined with three TM is greater than that of TM alone. Table 3 AUC of prediction probability by stepwise Logistic regression curve of single tumor marker and combination of three tumor markers (omitted)
2.5TM evaluation parameters According to ROC curve and stepwise Logistic regression, the sensitivity, specificity, Youden index (sensitivity+specificity-1) and positive likelihood ratio/negative likelihood ratio of each index were calculated (Table 4). Joint analysis: combined analysis with AFP, CEA and CA 199 with CA724 as the basic index. If any index exceeds the "critical value", it is defined as a gastrocolon tumor. The Youden index, positive likelihood ratio and negative likelihood ratio of CA724, CEA and CA 199 are the highest, giving consideration to sensitivity and specificity. Although the specificity of the combined method of other indexes has been improved, the sensitivity and other parameters have obviously decreased. Table 4 Diagnostic Efficiency of Combined Analysis of Tumor Markers in Gastrocolon Tumors (omitted)
3 discussion
CEA, AFP, CA724 and CA 199 have certain clinical value in the diagnosis of gastrointestinal malignant tumors [5]. CEA is a traditional tumor-associated antigen, which can be increased in all kinds of tumors in digestive tract. The results are reliable and stable, but the disadvantage is that its specificity is not high. In non-hepatogenic gastric and colon tumors, AFP concentration increased less than 265438 0%; CA724 belongs to glycoprotein carcinoid embryonic antigen, and its increase is related to tumor stage (such as Dukes grade). CA 199 is increased in many kinds of digestive tract adenocarcinoma [5-8].
ROC curve is a comprehensive reflection of sensitivity and specificity, taking benign and malignant diseases of stomach and colon as the research object, and taking sensitivity to false positive rate (1- specificity) as the curve. In this paper, ROC curve is drawn, AUC of different TM is compared, and "cut-off value" is provided according to AUC principle to ensure the biggest difference between benign diseases of gastrocolon and malignant tumors of gastrocolon [4]. Stepwise logistic regression is used for fitting. 0. 1) was rejected because its predicted value was relatively small. The ROC curve obtained in this way can directly reflect the fitting situation of the model in the geometric sense, and the fitting effect of the Logistic model can be quantitatively reflected by the area under the curve, so as to better evaluate the degree of conformity between the model goodness and the actual data [1-3]. The goodness of fit and prediction effect of the equation in this paper are ideal, and the AUC of the prediction probability ROC curve is 0.934.
At present, there are still some shortcomings in the application of TM, such as high missed diagnosis rate of single index, which has certain limitations in tumor screening and early diagnosis, but joint detection can make up for this deficiency to some extent [4-9]. Compared with the single item, the sensitivity of TM combination in this paper shows an upward trend, the specificity shows a downward trend, and Youden index shows an upward trend. The combination of A724+CEA+CA 199 is the best. Therefore, it is very necessary to carry out appropriate TM combined detection for tumor patients [9]. The value of joint analysis can be measured by stepwise logistic regression analysis [8]. Because AFP has little diagnostic value for gastric and colon tumors, it did not enter the regression model, and the other three indexes entered the Logistic regression model. This result is consistent with the analysis results of TM concentration in two groups (as shown in table 1). AUC and Youden index can comprehensively reflect the diagnostic ability of TM, so we reset the critical value according to ROC curve and the principle of maximum Youden index, and then make a joint analysis of single index and multi-index, and conclude that CA724 is the best single index for the study of gastric and colon tumors. In many joint analysis, the effect of CA724+CEA+CA 199 is the best, which is consistent with the results of stepwise Logistic regression model. However, the effect of logistic regression fitting model in this paper needs to be verified by pathological examination in a larger patient population. As for its evaluation of surgical treatment, chemotherapy and radiotherapy for gastric and colon tumors, prognosis judgment [6], tumor metastasis and whether it can be used as a curative effect evaluation alone [1
refer to
[1] Brannback LC, Pepe MS, Allonzot TA. Using ROC curve to measure the therapeutic effect in clinical trials [J]. Statistical Medicine, 2006,25 (4): 575-590.
[2] Molodinovitch K, Faraggi D, Reiser B. Comparing the area under two related ROC curves: parametric and nonparametric methods [J]. Journal of Biomedicine, 2006,48 (5): 745-757.
[3] Dodler and Pepe's partial AUC estimation and regression. Biostatistics.2003,59 (3): 614-623.
Yu Chuanhua. SPSS and statistical analysis [M]. Beijing Electronic Industry Press 2007:356-408.
[5] edited by Lothar Thomas, translated by Lv Yuan, Zhu, and others. Clinical laboratory diagnostics [M]. Shanghai: Shanghai Science and Technology Press, 2004, 579-682.
Ferroni P, Pamilo R, Spila A, et al. Prognostic value of carcinoembryonic antigen and vascular endothelial growth factor in colorectal cancer [J]. Oncology, 2006,71(3-4):176-184.
Lai, Li, Huang, et al. Comparison of serum levels of CA724, CEA, TPA, CA 199 and CA 125 in patients with gastric cancer and their correlation with recurrence [J]. Hepatogastroenterology, 2002: 49 (46):1/.
[8] Ms. Pepe, Cai T, Long Tong G. Classification based on receiver operating characteristic curve area combined with predictive factors [J]. Biometrics, 2006,62 (1): 221-229.
[9]Louhimo J, Kokkola A, Alfthan H, et al. Preoperative hCG and CA724 are prognostic factors of gastric cancer [J].Int J Cancer, 2004,11(6): 929-933.
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