Circulating miR-222 in plasma and its potential diagnostic and prognostic value in gastric cancer

Abstract

Previous studies have revealed the significance of circulating microRNAs as biomarkers for cancers. The aim of this study was to detect the levels of circulating microRNA-222 (miR-222) in plasma of gastric cancer (GC) patients and evaluate its diagnostic and prognostic value. Levels of circulating miR-222 were detected by using qRT-PCR in plasma of 114 GC patients, 36 chronic atrophic gastritis (CAG) patients and 56 healthy controls. The result showed that the expression of circulating miR-222 in plasma was significantly upregulated in GC compared with CAG and healthy controls (all at P < 0.001). And its high level was significantly correlated with clinical stages (P < 0.001) and lymph nodes metastasis (P = 0.009). The receiver operating characteristics (ROC) curve analyses revealed that miR-222 had considerable diagnostic accuracy, yielded an AUC (the areas under the ROC curve) of 0.850 with 66.1 % sensitivity and 88.3 % specificity in discriminating GC from healthy controls. Moreover, Kaplan-Meier analysis demonstrated a correlation between increased circulating miR-222 level and reduced disease-free survival (P = 0.016) and overall survival (P = 0.012). In multivariate analysis stratified for known prognostic variables, circulating miR-222 was identified as an independent prognostic marker. In conclusion, our findings suggested that circulating miR-222 in plasma might be a potential and useful noninvasive biomarker for the early detection and prognosis of GC.

Prognostic role of microRNAs in human gastrointestinal cancer: A systematic review and meta-analysis

“…Cut-off values of high or low miRs expression were mainly mean and median values. As for clinical endpoints, there were 46 studies [1, 2, 10–12, 16, 20, 22, 24–27, 29–33, 36–41, 43–59, 61–66] including overall survival (OS), 5 studies [67–71] including disease free survival (DFS) and another 9 studies [18, 19, 21, 23, 28, 34, 35, 42, 60] including both OS and DFS. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, miR-196b, miR-222, miR-106b, miR-500, miR-377, miR-25, miR-181a, miR-183, miR-1288, miR-106a-5p, miR-21, miR-30e, miR-142-3p, miR-1246, miR-508, miR-503, miR-942) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, miR-22, miR-217, miR-506, miR-133, miR-218, miR-137, miR-326, miR-486-5p, miR-29, miR-23b-3p, miR-194, miR-451, miR-34a, miR-106a, miR-143, miR-16, miR-139-3p, miR-361-5p, miR-365, miR-338-3p, miR-200c, miR-141, miR-150, miR-138, miR-134a, miR-195, miR-203, miR-375) correlated with poor prognosis in GIC patients (Table 1, Table 2).…”

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

“…When combining the high/low expression scores for the two miRNAs for each OS patient, the separation became even more distinct and significant, signifying the robustness of the miR-221/ 222 signature as a prognostic biomarker. Increased expression of miR-221 and miR-222 has also been shown to be significantly associated with lymphatic metastasis in gastric, colorectal, and breast cancer (Falkenberg et al, 2013;Fu et al, 2014;Liu et al, 2012b;Sun et al, 2011). Furthermore, these two miR-NAs have been shown to be a promising biomarker in breast cancer in function of time to developing distant metastasis, although a high expression of both miR-NAs was associated with poor prognosis in breast cancer (Falkenberg et al, 2013).…”

Plasma microRNA‐based signatures to predict 3‐year postoperative recurrence risk for stage II and III gastric cancer

“…miR-21 was one of the first miRNAs found in the human genome, and it stands out as the most commonly upregulated miRNA in various malignancies. 26 miR-126, miR-125b and miR-26a were involved in the pathogenesis of many cancers by different mechanisms, acting as oncogenes or tumor suppressor genes. 22 miR-148a can suppress tumor proliferation, invasion and metastasis in gastric cancer by regulating several target genes and pathways.…”

“…23 miR-222 was reported to promote cell proliferation by targeting RECK 24 and PTEN, 25 and increased plasma miR-222 level was an independent prognostic marker for reduced DFS and OS in 114 GC patients. 26 miR-126, miR-125b and miR-26a were involved in the pathogenesis of many cancers by different mechanisms, acting as oncogenes or tumor suppressor genes. 27,28 In GC, miR-26a suppressed GC growth and metastasis by targeting FGF9, 29 and circulating miR-26a in plasma was a potential marker for diagnosis in GC.…”