| [Background]Patients with pancreatic cancer have little opportunity of surgery and poor prognosis due to aggressive invasion and metastasis manner. Epithelial-Mesenchymal transition (EMT) plays critical role in tumor invasion and dissemination. The inability to monitor EMT process in circulation system leads to an incomplete understanding with only primary tumor and metastatic loci. Besides serving as "liquid biopsy", circulating tumor cells (CTCs) can also be used as a vital tool for studying EMT and make it possible to monitor the whole course of EMT in pancreatic cancer.[Objective]1. To assess the clinical application prospect of pancreatic CTC as "liquid biopsy".2. To detect epithelial and mesenchymal markers in primary tumor, peripheral blood CTCs and metastatic lymph nodes in pancreatic cancer respectively in order to analyze the whole course of EMT.[Methods]1. We conducted a classification count and dynamic monitoring of pancreatic CTCs by SET-iFISH, and analysis the different classification and their correlations with treatment, recurrence, metastasis, clinicopathologic factors and prognosis.2. We conducted a classification count and dynamic monitoring of pancreatic CTCs by microfluidic chips, and analysis the different classification, especially EMT status and its correlation with surgery, chemotherapy and clinicopathologic factors.3. E-cadherin and Vimentin were measured in primary tumor and metastatic lymph nodes through immunohistochemistry (IHC) with patients diagnosed as pancreatic ductal adenocarcinoma. Whole course of EMT in pancreatic cancer was described and the relationship between EMT status, clinicopathologic factors and prognosis were evaluated.[Results]1. SET-iFISH:63 blood samples in 27 individuals (20 pancreatic cancers,5 benign pancreatic tumors and 2 healthy individuals) were detected. CTC counts varied with surgery, chemotherapy and recurrence. Patients with CTMs before surgery had shorter OS (p=0.027) and PFS (p=0.015). The main composition of pancreatic primary tumor and metastatic ascites cells were epithelial cells, while majority of CTCs were non-epithelial cells.2. Microfluidic chip:46 blood samples in 24 individuals (22 pancreatic cancers and 2 healthy individuals) were detected and CTCs were divided into E, E>M, E=M, E<M and M types. Total CTC counts (p=0.005) and M type CTCs (p=0.000) decreased after surgery, while E type CTCs increased after chemotherapy (p=0.004), leading to an increase of mesenchymal CTC proportion. CTCs count was correlated with clinical staging, T staging and metastasis (p<0.05), but the EMT status was not significantly related to lymph node metastasis or perineural invasion in pancreatic cancer.3.27 patients with pancreatic cancer were included. There was a significant correlation between E-cadherin and differentiation (p=0.016) and decreased CA19-9 level (p=0.023); while Vimentin was related to lower differentiated level (p=0.016). The mean DFS in E>M group and E≤M group were 627.5±49.0 days and 337.1±80.9 days, respectively (χ2=4.867, p=0.027). Primary tumor and metastatic lymph nodes of pancreatic cancer mainly consisted of epithetial cells, while the proportion of epithitail and mesenchymal cells in CTCs were about 50% respectively.[Conclusions]1. Liquid biopsy:CTM was a valid predictor of poor prognosis. CTCs count was related to clinical staging, T staging and metastasis, and varied with surgery, chemotherapy and recurrence.2. Whole course of EMT:A trend of EMT/MET change was observed in pancreatic primary tumor, CTCs and metastatic lymph nodes. EMT was related to chemotherapy and poor prognosis, but the relationship between EMT and invasion/metastasis in pancreatic cancer need further research.
|
PDF Full Text Request