Abstract
Before reaching a peripheral vein (PV), miRNAs released by the tumor are diluted and dispersed throughout the body or even retained in a specific organ. We hypothesized that blood drawn from the tumor-draining vein could provide more homogeneous information than blood drawn from the PV as that blood would contain all the biomarkers released by the tumor before they reach a potential metastatic site. We have profiled 754 miRNAs in 15 colon cancer plasma samples from the tumor-draining vein, the mesenteric vein (MV), identifying 13 microRNAs associated with relapse. The prognostic impact of these miRNAs were validated in 50 MV and 50 paired PV plasma samples of stage I-III colon cancer patients. Four miRNAs, let-7g, miR-15b, miR-155 and miR-328, were found overexpressed in MV compared to PV, and patients with high levels of those miRNAs in MV plasma had shorter time to relapse. Interestingly, in patients developing liver metastases, the exosomal cargo of miR-328 was much greater in MV than in PV plasma indicating a possible role of miR-328 in the development of liver metastases. Our results indicate that in colon cancer, the primary tumor releases high concentrations of miRNAs through the MV, and some of them are contained in tumor derived exosomes.
Highlights
Colon cancer (CC) is the third most common cancer and the second cause of death from cancer in developed countries [1]
time to relapse (TTR) was 59.4 months for those with low levels of Figure 1: let-7g A., miR-15b B., miR-155 C. and miR-328 D. expression levels in plasma from the peripheral vein (PV) and paired mesenteric vein (MV) of colon cancer patients
Metastases are the primary cause of death in cancer patients
Summary
Colon cancer (CC) is the third most common cancer and the second cause of death from cancer in developed countries [1]. A recent study in serum samples found that the exosomal cargo of miR-17-92 cluster was associated with poor prognosis in metastatic patients with colorectal cancer [16], while another study in circulating exosomal miRNAs in metastatic colorectal cancer patients identified a set of completely different miRNAs that did not include the miR-17-92 cluster [17]. These inconsistent findings on miRNAs in tumor, biofluids, and exosomes in CC have been attributed to various causes, including different patient populations, internal controls, and laboratory methods [8]. We confirm that these miRNAs were contained in MV-exosomes
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