Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer

Abstract

Abstract. The aim of the present study was to ascertain whether plasma levels of specific microRNAs (miRNAs) are associated with distant metastasis (DM) in gastric cancer (GC). miRNA profiling was performed on 12 pairs of samples of gastric cancer with distant metastasis (GC/DM) and gastric cancer with no distant metastasis (GC/NDM); 14 differentially expressed miRNAs were identified for further inspection. Validation of these 14 miRNAs using quantitative reverse transcription PCR (qRT-PCR) on an independent validation set identified 2 differentially expressed miRNAs (miR-122 and miR-192). Further validation of these two candidate miRNAs was conducted in a disease control set, a self-paired plasma set and finally in gastric cell lines in vitro. The results revealed that when compared with GC/NDM and healthy controls (HCs), plasma levels of miR-122 were significantly lower and plasma levels of miR-192 were significantly higher in GC/DM samples (both P<0.01). The plasma miR-122 level was again lower and the plasma miR-192-level was again higher in patients with GC/DM than in patients with benign gastric ulcer (BGC) and chronic gastritis (CG) (P<0.01). Compared to the level in patients with pre-distant metastases, miR-122 was significantly decreased while miR-192 was markedly elevated in patients with post-distant metastases (P<0.01). In CTC105 and CTC141 cells, miR-122 levels were moderately lower and miR-192 levels were markedly higher when compared to the levels in the GES-1 cells. ROC analyses showed that the AUC for plasma miR-122 was 0.808 (95% CI, 0.712-0.905; P<0.01), and the AUC for plasma miR-192 was 0.732 (95% CI, 0.623-0.841; P<0.01) for distinguishing GC/ DM from GC/NDM. High expression of miR-122 in plasma independently contributed to a more favorable prognosis for GC (hazard ratio, 0.262; 95% CI, 0.164-0.816; P= 0.038; Cox regression analysis), whereas the miR-192 level was not associated with the overall survival time. Our results demonstrated that assessment of decreased circulating miR-122 and elevated circulating miR-192 levels has the potential to improve early detection of DM in GC. Higher plasma levels of miR-122 in GC may indicate a favorable prognosis.

Circulating microRNAs: potential biomarkers for common malignancies

“…The study by Chen et al [141] investigated if specific plasma miRNAs could be associated with distant metastasis. Their results identified that miR-192 levels were significantly higher in patients with a distal metastasis.…”

Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis

“…miRNAs are endogenous small (19-26 nucleotides) non-protein-coding RNAs that are reportedly linked to oncogenesis through their targeting of miRNAs for cleavage or translational repression [12,13]. Furthermore, accumulating evidence has discovered the aberrant expression of specific miRNAs in various malignant tumors, including GC [14][15][16][17][18][19]. In addition, miRNAs' characteristic of being stably detected in plasma/serum makes them promising molecular biomarkers for confirming early GC diagnosis after an initial screening or diagnostic test.…”

MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2

“…By contrast, miRNAs that are downregulated act as tumor suppressors during GC progression. These miRNAs generally exert their function via anti-proliferative and pro-apoptotic associated genes (14)(15)(16). Additionally, decreased levels of miR-144 in GC tissue may be associated with poor patient prognosis and it was demonstrated that the reintroduction of miR-144 increased the susceptibility of cancer cells to chemotherapy (17,18).…”