Dataset Information

Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma

ABSTRACT:

Background

Much importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC).

Methods

PDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis.

Results

CTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P<0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043).

Conclusions

Our research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.

SUBMITTER: Pan Y

PROVIDER: S-EPMC8582019 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.