| Objective To evaluate the current clinically commonly used gastric cancer serum tumor markers,and explore the potential value and clinical significance of exosomal circular RNAs(circRNAs)as new gastric cancer markers.Methods Serum samples from 260 patients with gastric cancer were collected as gastric cancer group A,and serum samples from 140 patients with benign gastric diseases were used as control group A to evaluate the traditional gastric cancer serum markers.Serum samples of 73 patients with gastric cancer were collected as gastric cancer group B,25 patients with benign gastric disease and 30 healthy patients were treated as control group B to investigate the changes of exosomal circRNAs.The electrochemiluminescence method was used to detect the changes of serum markers such as CA72-4,CEA,CA19-9,CA242,CA50 and CA125 in serum samples.Analyze the sensitivity and specificity of traditional serum markers such as the sensitivity and specificity of single detection and combined detection.Quantitative-time PCR(q RT-PCR)was used to detect the expression levels of exosomal circRNAs in serum samples.Transmission electron microscopy,nanoparticle analyzer and Western blot were used to identify the characteristics of the extracted serum exosomes.Analyze the expression levels of exosomal circRNAs and their relationship with the clinicopathological characteristics of gastric cancer patients,and evaluate the diagnostic value for gastric cancer by establishing a receiver operating characteristic curve(ROC).Results The concentrations of CA72-4,CEA,CA19-9,CA242,CA50 and CA125 in gastric cancer group A were significantly higher than those in control group A,and the differences were significant(t=5.799～8.826,P<0.05).CEA had the highest area under curve(AUC)value for single test(0.779),CEA had the highest sensitivity(52.31%),CA242 had the highest specificity(96.43%),and CEA had the highest accuracy(64.75%).The highest AUC value in the combined test was the CA72-4 + CEA + CA19-9 + CA242+ CA50 + CA125 group(0.928).The most sensitive were the CA72-4 + CEA + CA19-9 +CA242 + CA50 group and the CA72-4 + CEA + CA19-9 + CA242 + CA50 + CA125group(both 85.77%).The highest specificity was the CA72-4 + CEA + CA19-9 group(78.57%).The highest accuracy was the CA72-4 + CEA + CA19-9 + CA242 + CA50group(82.5%).The concentrations of CA72-4,CEA,CA19-9,CA242,CA50 and CA125 in gastric cancer group B were significantly higher than those in control group B,and the differences were significant(t=2.311～5.004,P<0.05).The AUC values of CA72-4,CEA,CA19-9,CA242,CA50,and CA125 for gastric cancer screening were 0.748,0.686,0.658,0.701,0.667 and 0.748,respectively.The AUC value of the combined detection of six serum tumor markers was 0.905.After transmission electron microscopy,nanoparticle analyzer and Western blot,the characteristics of exosomes have been verified.In preliminary experiments,the expression levels of serum exosomal circ PVT1 and has-circ-0010522 in patients with gastric cancer were significantly higher than those in patients with benign gastric disease and healthy subjects(t = 4.571 ～ 8.064,P < 0.05).There was no difference in the expression level of circ PVT1 and has-circ-0010522 between patients with benign gastric disease and those with healthy physical examination.Compared with the control group B,the expression levels of serum exosomal circ PVT1 and has-circ-0010522 in the gastric cancer group B were significantly increased(t = 11.364,6.467,P < 0.05).The AUC values of exosomal circ PVT1 and has-circ-0010522 for gastric cancer screening were0.916 and 0.798,respectively,and the AUC value of the combined detection of the two circRNAs was 0.933.The expression level of circ PVT1 was significantly correlated with gender,tumor diameter,TNM stage,lymph node metastasis and peritoneal metastasis(P<0.05).The expression level of has-circ-0010522 was significantly correlated with age and lymph node metastasis(P<0.05).The AUC value of circ PVT1 used to distinguish whether the tumor diameter is less than 5 cm is 0.778.The AUC value of circ PVT1 is0.808 when it is used to distinguish patients in stage Ⅰ～Ⅱ or stage Ⅲ～Ⅳ.The AUC value of circ PVT1 is 0.828 when it is used to distinguish whether the patient has peritoneal metastasis.The AUC values of circ PVT1 and has-circ-0010522 used to distinguish whether a patient has lymph node metastasis are 0.764 and 0.709,respectively.The combined detection of circ PVT1 and has-circ-0010522 is used to distinguish whether patients have lymph node metastasis.The AUC value is 0.809.Conclusion Preoperative detection of serum tumor markers commonly used in clinical practice is of great value for the diagnosis and condition judgment of patients with gastric cancer and exploring a more efficient and reasonable combination of detection will help improve the sensitivity and accuracy of diagnosis.Serum exosomal circ PVT1 and has-circ-0010522 were both significantly increased in patients with gastric cancer,which were correlated with the clinicopathological characteristics of gastric cancer,and had certain value for the diagnosis and differential diagnosis of gastric cancer.Moreover,combined detection could significantly improve the diagnostic efficiency,and had the possibility of being used as new tumor markers for gastric cancer. |
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