Differential MIR-21 Expression in Plasma From Mesenteric Versus Peripheral Veins

Abstract

Findings on the role of plasma miR-21 expression in colorectal cancer are contradictory. Before reaching a peripheral vein (PV), microRNAs released by the tumor are dispersed throughout the body. We hypothesized that blood drawn from the mesenteric vein (MV) near the site of the primary tumor could provide more homogeneous information than blood drawn from the PV.We have analyzed miR-21 expression in matched samples of tumor tissue, normal tissue, MV plasma, and PV plasma in 57 surgically resected patients with colon cancer and correlated our findings with clinical characteristics and disease-free survival (DFS).miR-21 expression was higher in MV than PV plasma (P = 0.014) and in tumor than in normal tissue (P < 0.001). Patients with high levels of miR-21 in MV plasma had shorter DFS (P = 0.05) than those with low levels, and those with high levels in both MV and PV plasma had shorter DFS than all other patients (P = 0.01).Our findings suggest that the primary tumor in colon cancer releases high concentrations of miR-21 in the MV but that these concentrations are later diluted in the circulatory system. MV expression of miR-21 may be a stronger prognostic marker than PV expression.

Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

“…High plasma levels of miR-21 in blood samples from both mesenteric and peripheral veins were associated with short disease-free survival. No validation was performed, and different patient classifications were used [ 20 ].…”

“…The choices of normalization methods were: global mean [ 30 ], spike in [ 26 ], stable miRNAs [ 28 ], and normalization using software from Applied Biosystems [ 27 ]. For the studies analyzing a small number of miRNAs, miR-16 was used in four studies [ 17 , 18 , 23 , 31 ], miR-191 in one study [ 20 ], RNU6B in one study [ 25 ], and spike in normalization in three studies [ 21 , 22 , 26 ].…”

Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver metastases in resected patients with colon cancer

“…For all 50 patients, we obtained paired MV and PV blood as previously described [ 18 ]. On the day of surgery, 5 mL of blood was drawn from the PV and stored in heparinized tubes.…”

“…For example, exosomal biomarkers released by a colon tumor may be retained in the liver and not continue their circulatory route to the forearm. In contrast, blood drawn from a mesenteric vein (MV) close to the tumor site may well contain all the biomarkers released by the tumor before they reach the potential metastatic site [ 18 ].…”

Expression Profiles and Clinical Significance of MicroRNAs in Papillary Renal Cell Carcinoma

“… 8 Furthermore, miRNAs are aberrantly expressed or mutated in human cancers, suggesting that they may exert critical functions as a novel class of tumor suppressive or carcinogenic factors. 9 – 13 The diagnostic and prognostic capabilities of miRNAs have been thoroughly explored in ccRCC, and the cancer-specific miRNA expression profiles have been identified, which were significantly associated with patient survival. 14 – 16 However, the clinical utility of miRNAs in pRCC remains to be elucidated.…”