| Objective:In order to compare the differences in the content of various variables in common female malignant tumors and to explore the evaluation value and clinical significance of tumor markers anomaly on molecular level tumor heterogeneity,we introduced a new cencept of specific tumor marker(STM)to extract specific antigens of tumor markers.The method we used was a combined detection of human epididymis protein 4(HE4)and female common malignant tumor markers carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199).Methods:A total of 58 cases of ovarian cancer,62 cases of benign ovarian tumor,60 cases of healthy control,and 64 other gynecological tumor patients(including 20 cases of breast cancer,33 cases of endometrial cancer,and 11 cases of fallopian tube cancer)were selected as the research subjects.The contents of CEA,AFP,CA125,HE4 and CA199 in each group were measured by combas e601,a fully automatic electrochemical luminescent immunoassay system produced by Roche,Switzerland.The maximumvalue of S/CO ratio in each group was calculated as STM(S was the sample test value,and CO was the cut-off value for the identification of individuals with tumor,namely the limit value of the normal reference range of each indicator).The ROC curve was used to determine the critical value,specificity and sensitivity of STM in differentiating health from ovarian cancer.The differences of CEA,AFP,CA125,HE4,CA199 and STM levels were compared in different groups of pathological histology.ROC curves were drawn for the above parameters according to the different groups of FIGO stages of ovarian cancer,and the diagnostic effects of each parameter on stage II,III and IV of ovarian cancer FIGO stages were compared.The difference in STM was compared for different groups of ovarian cancer differentiation.Results:A new diagnostic standard for ovarian cancer with a critical value of 1.00,sensitivity of 84.5%,and specificity of 90%(95%CI: 0.890 ~ 0.977,P<0.01)was provided by STM.CA125,HE4 and STM were significant in the diagnosis of FIGO stage II,III and IV ovarian cancer(P<0.05),with diagnostic thresholds of 103.72,135.30 and 2.41,respectively.CA125 and STM had better diagnostic efficiency,and the AUC was basically the same as 0.764 and 0.762,higher than the 0.668 of HE4.The highest sensitivity of STM was 72.7%,and the highest specificity of CA125 was 92.0%.It indicates that ovarian cancer stage FIGO II,III and IV can be predicted and diagnosed according to the criteria of CA125 > 103.7 and STM > 2.4.By comparing the levels of each parameter in different pathological tissues,STM detection values in the ovarian cancer group were significantly higher than those in the healthy control group and the ovarian benign tumor group,and both values were greater than 1.00,meeting the above diagnostic criteria for ovarian cancer.The highest expression of STM was 5.80 in serous ovarian cancer.Next was endometrioid ovarian cancer(2.29),followed by mucinous ovarian cancer(1.96),and transparent cell carcinoma(1.20).The STM of endometrial carcinoma and fallopian tube carcinoma ranged from 0.90 to 1.However,benign ovarian tumor,breast cancer and healthy control were nearly all around 0.50,and the difference was statistically significant(P<0.05).The results indicated that tumorheterogeneity in different histopathological types could be evaluated according to STM detection values.STM>1.00 was used as the standard for statistical positive rate.It was found that STM had a high positive rate in ovarian cancer,100% in mucinous ovarian cancer,89.2% in serous ovarian cancer,88.9% in endometrioid ovarian cancer,but only50% in transparent cell cancer.The positive rate of oviduct cancer and endometrial cancer was 45.5%,and that of breast cancer was only 5%.Benign ovarian neoplasms and healthy controls also had a small positive rate.This suggests that although benign ovarian neoplasms and healthy controls have no neoplastic histopathology at the gold standard of tumor diagnosis--pathological typing,there is a potential for conversion to ovarian cancer at the molecular level.There was no significant difference in STM detection value and positive rate in ovarian cancer differentiation groups(P>0.05).This indicated that STM test had little effect on differentiation degree of ovarian cancer.CEA test values were increased in breast cancer,but the increase was not significant.In various type of tumor heterogeneity,that difference in CEA positive rate was statistically significant(P < 0.05),but the difference was not obvious.The highest positive rate was 18.9% in serous ovarian cancer.There was no statistically significant difference between AFP detection value and positive rate(P>0.05),only slightly increased in transparent cell carcinoma,which may have some value in the auxiliary diagnosis of transparent cell carcinoma,to be proved by subsequent studies.CA199 significantly increased the detection value of mucinous ovarian cancer by 20.53,and the positive rate was as high as 50.0%,which may be of certain value for the auxiliary diagnosis of mucinous ovarian cancer.CA125 is up to 114.0 in serous ovarian cancer,with a high prevalence of 75.7%,which is elevated in both ovarian cancer groups.There were positive rates in healthy controls and in benign tumors,tubal and endometrial cancers.HE4 was highly expressed in the ovarian cancer group,and the detection value of serous ovarian cancer was 138.2,with a positive rate of 48.6%;the detection value of mucinous ovarian cancer was 109.31,with a positive rate of 25.0%.HE4 was defined as greater than 140,and no positive cases were found in the healthy control group,ovarian benign tumors,transparent cell carcinoma,fallopian tube carcinoma and endometrialcarcinoma.Conclusion:As a new indicator for the extraction of tumor marker specific antigen,STM has high sensitivity and specificity in the diagnosis of ovarian cancer,and it can be used to evaluate the molecular level of tumor heterogeneity in different pathological tissue types.CA125 and STM have better diagnostic efficacy in ovarian cancer FIGO II,III and IV.It provides the basis for accurate medical diagnosis,improves the effect of molecular targeted therapy,and improves the quality of life of patients. |
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