Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer

Abstract

Background Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC). Methods We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay. Results (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P \ 0.0001). The value of the area under the receiver-operating characteristic curve was 0.8059. (3) The plasma miR-18a levels were significantly reduced in postoperative samples compared to in preoperative samples (P = 0.0002). In an miR-18a overexpressing cell line, the miR-18a concentration of cultured medium increased in both cell number and time-course dependent manners, suggesting microRNA might be released from cancer cells into the surrounding environment. Conclusions Circulating miR-18a could be a useful biomarker for screening GC and monitoring tumor dynamics.

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

“…Furthermore, some extracellular miRNAs occur not only through cell lysis but also through active secretion [25][26][27] and can function as intercellular transmitters 19,26,28,29 . Thus, various blood-based miRNAs have been identified, including those in this study, and can be used for cancer detection, monitoring tumor dynamics, and predicting prognosis and chemoresistance [30][31][32][33][34][35][36][37][38][39][40][41][42] . Recently, Kosaka and Ochiya et al suggested a novel mechanism -that miRNAs could facilitate the system of maintenance and surveillance against cancer progression.…”

The correlation of circulating pro‐angiogenic miRNAs’ expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer

“…MiR‐17‐5p, as one of the frequently studied pro‐angiogenic miRNAs, is revealed to be elevated in cancer tissues and serum of GC patients and correlates with poor differentiation as well as higher TNM stage, which could promote GC cells’ proliferation and migration via several ways including posttranscriptional modulation of p21 and TP53INP1, transforming growth factor‐β receptor 2, and so on 34, 49, 50, 51. Another pro‐angiogenic miRNA (miR‐18a) is also observed to be raised in GC tissues compared with normal gastric tissues and is significantly correlated with higher pathological grade as well as lymph node status 52, 53. As with miR‐20a, it has been reported to be overexpressed in GC tissues and cells and positively correlates with tumor size, infiltration, and clinical grade, and it enhanced GC cells’ proliferation, migration, and invasion by regulating FBXO31, EGR2 54, 55, 56.…”

Circulating microRNA profiles in plasma: identification of miR-224 as a novel diagnostic biomarker in hepatocellular carcinoma independent of hepatic function

“…Moreover, compared to serum, plasma might retain higher protein levels, including those of coagulant-related proteins. These finding prompt us to consistently use plasma miRNAs in future clinical application [25,[34][35][36][37][38][39][40][41][42][43][44]. Indeed, miRNA profiles and miRNA concentrations were considerably different between serum and plasma.…”

“…These findings have prompted the identification of novel liquid biomarkers of miRNAs in cancers. We have previously identified cancer-associated miRNAs in plasma, which might be useful for the detection of cancer, monitoring of tumors, prediction of malignant potential, and prognosis and chemoresistance in gastric, esophageal and pancreatic cancers [25,[34][35][36][37][38][39][40][41][42][43][44].…”