CTCs Combined With CA199 Contribute To The Early Diagnosis Of Pancreatic Cancer

Objective: Pancreatic cancer(PDAC)is the fourth leading cause of cancer-related death,and its prognosis is the worst among tumors.The overall five-year survival rate is less than8%.Early diagnosis can improve the five-year survival rate of pancreatic cancer from 3%to 37%.Among the serum markers,CA19-9 is not ideal in diagnosis,and is prone to obtain false test results.CTCs are cancer cells detached from tumor sites,either primary or metastatic,which are responsible for dissemination and relapse of malignancy through circulation.This study explored whether CTCs can be used to supplement or replace CA199 in diagnosis of patients with pancreatic cancer.Methods: 134 eligible patients were enrolled from 2019.08 to 2020.08 in our hospital,comprising of 102 patients with pancreatic mass(80 patients with pancreatic cancer and22 patients with benign pancreatic tumor)and 32 patients with acute pancreatic cancer.In addition,34 healthy controls are involved.All subjects were collected 3.2ml whole blood for CTC detection and 3ml whole blood for CA19-9 detection.Results: The cells with CD45-/DAPI+/CEP8>2 were defined as CTCs.There was no significant difference between the positive rates of CTC number,CTC subtypes and tumor size,age,sex,location,differentiation,lymph node metastasis,distant metastasis,tumor stage and CA199 positive rate in patients with pancreatic cancer.The cut-off value of the number of CTC is 2 CTCs /3.2 ml,with a sensitivity of 76.3% and a specificity of 94.3%.The cut-off value of the CTC subtype is 2/ 3.2ml,with a sensitivity of 40.0% and a specificity of 98.9%.When the cutoff value of CA199 is 67,the sensitivity is 71.3% and the specificity 93.2%.When CA199 is combined with CTC for diagnosis,the sensitivity is 91.3% and the specificity is 90.9%.The combined panel greatly improves the sensitivity of detection at the cost of little reduction in specificity.In the comparison of the area under the curve,there was no significant difference between CTC number(AUC=0.846)and CA199(AUC=0.844)(P = 0.9759),but the AUC of CTC subtype(AUC=0.732)was significantly smaller than CA199 and CTC number(P=0.0191 and <0.0001,respectively).The AUC of the combined panel is 0.954,which was significantly higher than the AUC of CA199 and CTCs numbers.Conclusion: The number of CTC is a clinical predictor not inferior to CA199.In general,the sensitivity is increased from 71.3% to 91.3%,and the specificity is slightly reduced from 93.2% to 90.9%.CA199 supplemented by CTC contributes to the better diagnosis of PDAC.CTC subtype is a weaker diagnostic index than the number of CTC and CA199.When CTC is positive,CTC subtype cannot improve the diagnostic accuracy.The number and subtype of CTC detection can only distinguish benign from malignant disease,but not early from late.Further investigations are needed to verify our conclusions in large cohort.