| BACKGROUND AND AIMS Gastric cancer is one of the common malignanttumors in the worldwide, which has higher incidence rate and mortalityrate, and it threats our people’s health seriously. According to a largenumber of epidemiological data show that prognosis of advanced cancer ispoor, the rate of5-year survival rate is less than20%;while prognosisof early gastric cancer is good, the rate of5-year survival rate is upto90%. Therefore, gastric cancer is diagnosed early and accurate, whichis of great importance to improve poor prognosis and reduce mortality.Currently, the ways of diagnosis in early gastric cancer is numerous, suchas tumor markers (including carcino-embryonic antigen, carbohydrateantigen199, carbohydrate antigen50, serum pepsinogen, MG7antigen, etc),a variety of imaging techniques(including ordinary gastroscopy,endoscopic ultrasonography, magnifying endoscopy, NBI andchromoendoscopy, etc). Nevertheless, endoscopy, surgery combined withhistopathological examination is always the gold standard for thediagnosis of early gastric cancer. Because of our large population base,poor medical technology, and uneven distribution of medical resources, the detection rate of early gastric cancer is still low. Tumor markersare always directly synthesized or secreted by the tumor cells, or tumorclosely related active substance produced by other organizations, whichexist in tumor cells or the host of body fluids (including blood and serousmembrane fluid). Serological tumor markers have many advantages, such asconvenient, fast, easy to be accepted by patients and so on. But we stilllack of tumor markers which has high sensitivity and specificity indiagnosis of early gastric cancer. Macrophage inhibitory cytokine-1andUL16binding protein-2are the two factors found in the development ofproteomics. A large number of studies show that MIC-1and ULBP-2have aclose relationship in the development of a wide variety of tumors. Theresearch is to explore the diagnostic value of peripheral serum MIC-1andULBP-2for gastric cancer especially for early gastric cancer by comparedwith CEA and CA199, which are tumor markers by recognized in clinic.METHODS132upper gastrointestinal patients’ data of out-patientdepartment and in-patient department in the General Hospital of NingxiaMedical University from July2012to May2013were collected.34of themwere chronic non atrophic gastritis,33of them were chronic atrophicgastritis,24of them were early gastric cancer (which included the severeatypical hyperplasia), while41patients were with advanced gastriccancer. Then to determine the concentration of serum MIC-1and ULBP-2ofall patients by ELLSA experiment, and the concentration of CEA and CA199 are determined by ECL experiment. The concentration of MIC-1and ULBP-2in four groups are compared in pairs by rank test. We will evaluate thediagnostic AUC、sensitivity、specificity and accuracy in gastric cancerby drawing receiver operating characteristic, and the critical value isdetermined by ROC. According to critical value, we will evaluate thediagnostic sensitivity、specificity and accuracy in early gastric canerand advanced gastric cancer, in order to judge the value of early diagnosisof gastric cancer and advanced gastric cancer.74cases paraffin blocksof pathological tissue are extracted from132patients enrolled. In74cases,20of them were chronic gastritis (including10cases chronic nonatrophic gastritis and10cases chronic atrophic gastritis),24of themwere early gastric cancer,30of them were advanced gastric cancer. Wewill analyze the positive expression rate of MIC-1,ULBP-2in the tissueof chronic gastritis, early gastric cancer and advanced gastric cancerby IHC experiment. And we will use chi-squared test to analyze thedifference of the positive expression rate of two factors in three groups.RESULTS1. MIC-1and Gastric cancer1.1. The positive expression of MIC-1in tissue cellsThe positive expression of MIC-1in early gastric cancer andadvanced cancer is58.3%and73.3%, significantly higher than chronicgastritis (including chronic non atrophic gastritis and chronicatrophic gastritis)25.0%（Ｘ2=4.940，P=0.026；Ｘ2=11.286，P=0.001）. The positive expression of MIC-1had no significant difference between earlygastric cancer and advanced cancer（Ｘ2=1.350，P=0.245）.1.2. The concentration of serum MIC-1in chronic non atrophic gastritis,chronic atrophic gastritis, early gastric cancer and advanced gastriccancerThe concentration of serum MIC-1in early gastric cancer is722.6pg/ml, significantly higher than the chronic non atrophic gastritis501.6pg/ml, chronic atrophic gastritis513.4pg/ml(P=0.001, P=0.000).The concentration of serum MIC-1in advanced gastric cancer is733.7pg/ml, significantly higher than the chronic non atrophic gastritis,chronic atrophic gastritis (P=0.000,0.000). The concentration of MIC-1had no significant difference between chronic non atrophic gastritisand chronic atrophic gastritis (P=0.707). The concentration of MIC-1had no significant difference between early gastric cancer and advancedcancer (P=0.447).2. ULBP-2and Gastric cancer2.1. The positive expression of ULBP-2in tissue cellsThe positive expression of ULBP-2in early gastric cancer andadvanced cancer is62.5%and66.7%, significantly higher than chronicgastritis (including chronic non atrophic gastritis and chronicatrophic gastritis)30.0%（Ｘ2=4.619，P=0.032；Ｘ2=6.464，P=0.011）. The positive expression of ULBP-2had no significant difference between earlygastric cancer and advanced cancer（Ｘ2=0.102，P=0.75）.2.2. The concentration differences of serum ULBP-2in chronic non atrophicgastritis, chronic atrophic gastritis, early gastric cancer and advancedgastric cancerThe concentration of serum ULBP-2in early gastric cancer is43.0pg/ml, significantly higher than the chronic non atrophic gastritis27.6pg/ml, chronic atrophic gastritis28.2pg/ml (P=0.005, P=0.003). Theconcentration of serum ULBP-2in advanced gastric cancer is49.4pg/ml,significantly higher than the chronic non atrophic gastritis, chronicatrophic gastritis (P=0.000,0.000). The concentration of ULBP-2had nosignificant difference between chronic non atrophic gastritis and chronicatrophic gastritis (P=0.865). The concentration of ULBP-2had nosignificant difference between early gastric cancer and advanced cancer(P=0.264).3. The diagnostic critical values of serum MIC-1,ULBP-2,CEA,CA199ingastric cancer are574.3pg/ml,33.7pg/ml,5.0ng/ml,27.0U/L，and thediagnostic sensitivity are86.6%,78.5%,34.4%,37.5%, and the diagnosticspecificity are82.1%,76.1%,97.0%,95.5%,and the diagnostic accuracyare83.3%,77.3%,65.9%,67.7%,and the diagnostic AUC are0.878,0.804,0.686,0.673. 4. The diagnostic sensitivity,specificity and accuracy of serumMIC-1,ULBP-2,CEA,CA199in early gastric cancer and advanced cancerThe diagnostic sensitivity of serum MIC-1,ULBP-2,CEA,CA199in earlygastric cancer are79.2%,75.0%,20.8%,25.0%,and the diagnosticspecificity are82.1%,76.1%,97.0%,95.5%,and the diagnostic accuracy are81.3%,75.8%,76.9%,76.9%.The diagnostic sensitivity of serum MIC-1,ULBP-2,CEA,CA199in advanced gastric cancer are82.9%,80.5%,41.5%,43.9%,and the diagnostic specificity are82.1%,76.1%,97.0%,95.5%,and thediagnostic accuracy are82.4%,77.8%,75.9%,76.9%.5. The diagnostic sensitivity,specificity and accuracy of uniting serumMIC-1,ULBP-2,CEA,CA199in early gastric cancer and advanced gastriccancerThe diagnostic sensitivity and specificity of uniting serumMIC-1,CEA,CA199in early gastric cancer are91.7%and80.2%,and thediagnostic accuracy is83.5%. The diagnostic sensitivity and specificityof uniting serum ULBP-2,CEA,CA199in early gastric cancer are87.5%and79.1%,and the diagnostic accuracy is81.3%.The diagnostic sensitivity andspecificity of uniting serum MIC-1,CEA,CA199in advanced gastric cancerare92.7%and80.2%,and the diagnostic accuracy is85.2%. The diagnosticsensitivity and specificity of uniting serum ULBP-2,CEA,CA199in advancedgastric cancer are90.2%and79.1%,and the diagnostic accuracy is83.3%. CONCLUSION1. The positive expression of MIC-1, ULBP-2in early gastriccancer and advanced cancer are significantly higher than chronicgastritis.The concentration level of serum MIC-1, ULBP-2in early gastriccancer and advanced gastric cancer are significantly higher than chronicgastritis.2. Compared with wide accepted factors CEA and CA199in clinic, serum MIC-1,ULBP-2in early gastric cancer and advanced gastric cancer have higherdiagnostic value. MIC-1and ULBP-2might be a new serum marker for gastriccancer especially for early gastric cancer.3. Compared with individual factors, uniting serum MIC-1,ULBP-2,CEA andCA199has higher diagnostic value. |
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