Gene expression profile of circulating tumor cells isolated from pancreatic ductal adenocarcinoma patients

The incidence of pancreatic ductal adenocarcinoma (PDCA), an aggressive and lethal disease characterized by 5-year survival less than 5%, is increasing. The late diagnosis and the early metastatic spread are responsible for the poor prognosis. In addition, the majority of patients do not respond in a long-lasting and effective way to radio or chemotherapy. Circulating tumor cells (CTC) and CTC microemboli, considered to be responsible for the development of metastases, were detected in blood samples from PDCA patients and this detection appears to be clinically relevant. In fact, CTCs presence is associated with poor progression-free survival (PFS) and overall survival (OS). Moreover, the recurrence occurs earlier in patients with CTCs than those without, suggesting that CTCs are involved in pancreatic cancer malignancy. Little is known about the molecular profile of pancreatic CTCs. Thus, we evaluated in CTCs isolated from patients with metastatic PDCA, the expression of different markers involved in several pathways by using Digital Droplet PCR, to correlate the gene expression profile with clinical parameters, before and after the conventional chemotherapeutic treatment. At first, we found that the expression levels of ALCAM SHH, ZEB2, PATCH1/2, EPCAM, VIM, ICAM, POU5F1B and STAT3 are significantly higher in CTCs respect to those found in PDCA primary biopsies. Then, our findings demonstrated that high expression levels of ALCAM, POU5F1B and SMO are predictive of poor OS and PFS before and after palliative chemotherapy. Similarly, increased ALCAM/CD166 expression is an independent prognostic factor for poor survival, early tumor relapse and chemoresistance. Moreover, correlation analysis identifies two specific gene signatures in CTCs: the VEGF-A/EPCAM/NOTCH1/IHH and the ALCAM/CD44/POU5F1B/VEGF-B found in patients before and after the first line chemotherapy, respectively. Overall these data suggest that the multi-marker analysis of CTCs could represent a promising starting point to better select a personalized therapy in PDCA patients.