Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications

Abstract

The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients. Pancreatic cancerPancreatic cancer is the fourth leading cause of cancer-related death in Western countries, with a patient survival rate that is among the worst of any solid cancer. The most prominent risk factors are a family history of pancreatic cancer and cigarette smoking.

Clinical Significance of Circulating Tumor Microemboli as a Prognostic Marker in Patients with Pancreatic Ductal Adenocarcinoma

“…The common approaches for detection of CTCs in patients with PDAC include (a) immunological assays using antibodies directed against cell surface antigen, (b) technologies based on physical or biological properties of cancer cells, and (c) PCR-based molecular assays for tumor-derived DNA or RNA extraction from CTCs (11 ). Most of the current reported platforms usually detect small numbers of CTCs in late-stage PDAC.…”

“…The number of CTCs in patients with breast cancer is an independent predictor of progression-free survival (PFS) and overall survival (OS) (7 ). The clinical implications of CTCs in PDAC have not been proven to be indicative as in other cancers (11 ). Circulating tumor microemboli (CTM) have been reported to be associated with prognosis of small cell lung cancer (12,13 ).…”

Peripheral ENO1-specific T cells mirror the intratumoral immune response and their presence is a potential prognostic factor for pancreatic adenocarcinoma

“…Therefore, cytotoxic ENO1-specific Tcc that reach the tumor could be subsequently modified and switched off by different immunosuppressive mechanisms including PD-1/PD-L1 (41,42). However, because of the retained cytotoxic ability and potential antitumor function of peripheral ENO1-specific Tcc, they could be very important for the elimination of cancer-circulating cells and prevention of metastasis and disease relapse (47,48) (Fig. 5).…”

Pancreatic cancer: from bench to bedside

“…Researchers from the London cancer research center test blood from 191 patients with pancreatic cancer, identified 14 different genes, including BRCA gene mutation, they can greatly increase the chances of pancreatic cancer, and men may soon be able to predict the risk of pancreatic cancer by genetic testing. In epigenetic, Tjensvoll et al (15) found that early stage pancreatic cancer exist SLC32A1, CSMD2 and TRH methylation. Cote (16) expressed through measuring the level of microRNAs molecules circulating in the blood can help determine whether the patient is suffering from pancreatic cancer.…”