miR-203a-3p and MMP-2 protein are highly expressed in circulating tumor cells from patients with pancreatic carcinoma

Abstract

Objectives: to explore the morphological, molecular and phenotypical characteristics of circulating tumor cells (CTCs) from blood of patients with pancreatic carcinoma, and to correlate the findings with response to treatment, progression-free survival, overall survival (OS) and deep vein thrombosis (DVT). Methods: peripheral blood (10mL) was analyzed before the beginning of treatment, and after 60 and 120 days. CTCs were detected by ISET® and characterized by immunocytochemistry. For miRNAs analysis, peripheral leukocytes from the same patients and healthy individuals (controls) were collected in parallel at baseline. The expression of miRNAs was evaluated (in pool) using TaqMan™ Array Human MicroRNA Cards v2.0. Results: there were included 9 patients. The proteins MMP2 and TGFβ-RI were highly expressed (77.7%) in CTCs at baseline; at the first follow-up, MMP2 was predominant (80%) and at second follow-up, MMP2 and vimentin were predominant (50%). Circulating tumor microemboli (CTM) were found in two patients and both presented DVT. The miR-203a-3p was highly expressed in CTCs. miR-203a-3p is involved in the stimulation of epithelial-to-mesenchymal transition (EMT) and related to worse OS in pancreatic cancer (TCGA data). Conclusion: Due to the low number of patients and short follow-up, we did not observe a correlation between CTCs and response to treatment. However, there was a correlation between CTM and DVT as also miR-203a-3p was highly expressed in CTCs, corroborating the findings of EMT proteins. This study opens perspectives concerning the dynamic change in the pattern of proteins expressed along treatment and the use of miRNAs as new targets in pancreatic carcinoma.

miR‐203a—A multifaceted regulator modulating cancer hallmarks and therapy response

“…It stimulates the EMT potential of tumor cells and can serve as a new target in PC treatment. 64 miR-203a-3p abrogated invasion and migration in HT29 CRC cells and increased apoptosis. Subsequently, miR-203a-3p was found to target thrombospondin 2 (THBS2), through which it possibly regulates cancer progression.…”

“…MiR‐203a‐3p was also upregulated in circulating tumor cells isolated from patients with pancreatic ductal adenocarcinoma (PDAC). It stimulates the EMT potential of tumor cells and can serve as a new target in PC treatment 64 . miR‐203a‐3p abrogated invasion and migration in HT29 CRC cells and increased apoptosis.…”