| Background:With the aging of the population and the change of life style,cancer has become one of the main causes of death in China.According to the survey,standardized cancer incidence rate in China is 201.7/100,000,ranking 68 th in the world.At the same time,the standardized cancer mortality rate in China is 130.1/100,000,ranking the 12 th in the world.Esophageal squamous cell carcinoma(ESCC)is a kind of malignant tumors with high incidence and high mortality in China,of which earlier symptom was atypical.It is often diagnosed in the late stages,which results in poor long-term prognosis.Surgery is the main method for ESCC therapy.With the development of minimally invasive operation,thoracoscopic esophagectomy has been used more and more widely.Radiotherapy and chemotherapy treatments can be used for inoperable patients,which can effectively shrink the tumor and reduce the risk that it will metastasize.Biotherapy and targeted therapy have also shown effect in improving the condition.In recent years,endoscopic local injection chemotherapy and endoscopic ablation have shown good safety and application prospects.Early intervention can significantly improve 5-year survival,and endoscopic minimally invasive resection or ablation are potential therapeutic strategies for early ESCC.Endoscopy is a primary diagnostic technique for early detection of ESCC,but its invasiveness,severe side effects,and dependence on the skill of endoscopists limit its widespread use.The simple blood test is easier to be accepted by people,which has broad clinical application prospects.Tumor markers(tumor marker,TM)exist in in peripheral blood,other body fluids or tissues of tumor patients,closely related to the occurrence and development of malignant tumors.TM are mainly classified into tumor embryonic antigens,sugars and glycoproteins,ectopic hormones,enzymes and isoenzymes,tumor antigens,oncogenes and tumor suppressor gene protein products,etc.They can be useful in assisting the clinical diagnosis,monitoring recurrence or evaluating the efficacy and prognosis of malignant tumors,detected by radioimmunoassay,fluorescent labeled probes,immunofluorescence,enzyme-linked immunosorbent assay,chemiluminescence immunoassay,time-resolved fluorescence immunoassay,etc.The ideal TM should have high sensitivity and specificity,and can be used for accurate diagnosis and differential diagnosis of tumor.Currently,ideal TM for ESCC has not been found,and tumor markers such as squamous cell carcinoma antigen(SCC)and cytokeratin-19-fragment(Cyfra21-1)are commonly used in clinical diagnosis of ESCC.Therefore,Identification and validation of non-invasive blood-based tumor markers and development of effective screening and examination strategies are conducive to detection of early ESCC so as to improve early diagnosis and survival.Objective:To optimize serological diagnostic scheme of esophageal squamous cell carcinomas(ESCC)and provide the basis for further research on the noninvasive diagnosis of early ESCC,the expression level of clinical serum tumor markers in ESCC patients and healthy population was retrospectively studied.Combined with clinical characteristics,the value of clinical serum tumor markers in the diagnosis of ESCC was analyzed by means of statistical methods.Methods:The expression level of clinical serum tumor markers in ESCC patients and healthy population was retrospectively studied.Combined with clinical characteristics,the value of clinical serum tumor markers in the diagnosis of ESCC was analyzed by means of statistical methods.Retrospectively collect clinical information.ESCC group included age at diagnosis,clinical stage,pathological analysis,and expression level of carcinoembryonic antigen(CEA),alpha fetoprotein(AFP),carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)and Cyfra21-1,neuron-specific enolase(NSE),SCC,β2-microglobulin.The healthy population included age and the expression level of the same tumor markers as ESCC.SPSS 26.0 software was used for statistical analysis,and P<0.05 was considered significant statistically.The differences in the expression of serum tumor markers between ESCC and healthy population,and between ESCC subgroups were analyzed by statistical tests.A logistic regression model was then used to perform predictive analysis.Receiver operating characteristic curve was used to describe the diagnostic efficacy of single clinical serum tumor markers and combined schemes for ESCC.Results:1.Compared with healthy population,the expressions of CA199,Cyfra21-1,SCC and β2-microglobulin in ESCC were significantly increased,with statistical significance(P<0.05).In the diagnosis of early ESCC,there were no statistical differences in the expressions of these tumor markers(P>0.05);in the diagnosis of advanced ESCC,the expressions of CEA,CA199,Cyfra21-1,SCC,β2-microglobulin were significantly increased,with statistical significance(P<0.05).In addition,compared with the early ESCC,the expressions of CEA,Cyfra21-1,SCC and β2-microglobulin in the advanced ESCC were significantly increased,with statistical significance(P<0.05).2.Compared with healthy population,the expressions of SCC and β2-microglobulin in ESCC without lymph node metastasis were significantly increased,with statistical significance(P<0.05).The expressions of Cyfra21-1,SCC and β2-microglobulin in ESCC with lymph node metastasis were significantly increased,with statistical significance(P<0.05).In addition,compared with the ESCC without lymph node metastasis,the expression of CA199 was significantly increased in the ESCC with lymph node metastasis(P=0.002),with statistical significance(P<0.05).3.In the diagnosis of single tumor marker to ESCC,the diagnostic efficiency of each was low.When the specificity of CA199,SCC and β2-microglobulin was90%,the sensitivities were 20%,35.8% and 25% respectively(P<0.05).In the early diagnosis of ESCC,the diagnostic efficiency of each was poor(P>0.05);in the diagnosis of advanced ESCC,the diagnostic efficiencies of several tumor markers were improved.When the specificity of CA199,Cyfra21-1,SCC and β2-microglobulin was 90%,the sensitivities were 22.58%,29.03%,46.8% and 32.26%respectively(P<0.05).4.In the diagnosis of the combined assay of serum tumor markers to ESCC,joint detections of CA199+SCC+β2-microglobulin,CA199+Cyfra21-1+SCC+β2-microglobulin and eight serum tumor markers had high diagnostic value,and sensitivities were 40.83%,35% and 38.33% respectively with specificity of 90%(P<0.05).In the early diagnosis of ESCC,the sensitivity of joint detections of eight serum tumor markers was 22.41% with specificity of 90%(P<0.05).Compared with diagnostic efficiency of single serum tumor marker,the efficacy of early ESCC had improved,but the diagnostic value is still not high.In the diagnosis of advanced ESCC,joint detections of CA199+SCC+β2-microglobulin,CEA+CA199+SCC+β2-microglobulin,CEA+Cyfra21-1+SCC+β2-micro-globulin,CEA+CA199+Cyfra21-1+SCC+β2-microglobulin and eight serum tumor markers showed high diagnostic value,and sensitivities were 59.68%,56.45%,54.84%,56.45%,56.45%,respectively with specificity of 90%(P<0.05).Conclusion:1.The expressions of CA199,Cyfra21-1,SCC and β2-microglobulin in ESCC were significantly increased.CA199,SCC and β2-microglobulin had diagnostic value.The combination of CA199+SCC+β2-microglobulin had the highest diagnostic value.There were statistical significances in the comparison of all above indexes(P< 0.05).2.In the group without lymph node metastasis of ESCC,the expressions of SCC and β2-microglobulin were significantly increased.While in the group with metastasis,the expressions of Cyfra21-1,SCC and β2-microglobulin were significantly increased.Compared with the non-metastatic group,the expression of CA199 was significantly increased in the metastatic group.There were statistical significances in the comparison of all above indexes(P< 0.05).3.There was no statistical difference in the expression level and AUC of single tumor markers in early ESCC.The combination of eight items had diagnostic value.There were statistical significances in the comparison of all above indexes(P<0.05).4.The expressions of CEA,CA199,Cyfra21-1,SCC and β2-microglobulin in late ESCC group were significantly increased.CA199,Cyfra21-1,SCC and β2-microglobulin had diagnostic value.The combination of CA199+SCC+β2-microglobulin had the highest diagnostic value.There were statistical significances in the comparison of all above indexes(P< 0.05). |
