Plasma microRNAs, miR-223, miR-21 and miR-218, as Novel Potential Biomarkers for Gastric Cancer Detection

Abstract

BackgroundMicroRNAs (miRNAs), endogenous small non-coding RNAs, are stably detected in human plasma. Early diagnosis of gastric cancer (GC) is very important to improve the therapy effect and prolong the survival of patients. We aimed to identify whether four miRNAs (miR-223, miR-21, miR-218 and miR-25) closely associated with the tumorigenesis or metastasis of GC can serve as novel potential biomarkers for GC detection.MethodologyWe initially measured the plasma levels of the four miRNAs in 10 GC patients and 10 healthy control subjects by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients. Finally, the presence of miR-223, miR-21 and miR-218 in the plasma was validated in 60 GC patients and 60 healthy control subjects, and the areas under the receiver operating characteristic (ROC) curves of these miRNAs were analyzed.ResultsWe found that the plasma levels of miR-223 (P<0.001) and miR-21 (P<0.001) were significantly higher in GC patients than in healthy controls, while miR-218 (P<0.001) was significantly lower. The ROC analyses yielded the AUC values of 0.9089 for miR-223, 0.7944 for miR-21 and 0.7432 for miR-218, and combined ROC analysis revealed the highest AUC value of 0.9531 in discriminating GC patients from healthy controls. Moreover, the plasma levels of miR-223 (P<0.001) and miR-21 (P = 0.003) were significantly higher in GC patients with stage I than in healthy controls. Furthermore, the plasma levels of miR-223 were significantly higher in GC patients with helicobacter pylori (Hp) infection than those without (P = 0.014), and significantly higher in healthy control subjects with Hp infection than those without (P = 0.016).ConclusionsPlasma miR-223, miR-21 and miR-218 are novel potential biomarkers for GC detection.

microRNA detection in feces, sputum, pleural effusion and urine: Novel tools for cancer screening (Review)

“…Although many studies have reported the close relationship between plasma miRNAs and cancer, one plasma miRNA has been shown to be altered in multiple types of cancers [e.g. changes in miR-21 in the plasma can potentially indicate colorectal cancer (134) and gastric cancer (135)], which makes the diagnostic value lower than the four materials we listed previously. We did not put much emphasis on the blood biomarker limitations we discussed (low sensitivity, scarce quantity, complex nature and lack of reproducibility).…”

Blocking of STAT3 activation by miR-491, acting via EGFR, is involved in metastasis of hepatocellular carcinoma cells through inhibiting cancer stem cell-like properties

“…To determine the relationship between miR-491 and malignant potential, we used HepG2 and MHCC97H cell lines for knockdown and overexpression of miR-491, respectively. miRNAs have the capacity to inhibit translation and to induce mRNA degradation, predominantly through targeting of the 3′-UTRs of mRNAs [31]. In ovarian carcinomas, miR-491-5p binds to the EGFR 3′-UTR to mediate a repressive effect on protein expression [24].…”

Reduced miRNA-218 expression in pancreatic cancer patients as a predictor of poor prognosis

“…Recent studies have demonstrated that miR-218 is downregulated in various types of cancer, including cervical cancer, gastric cancer, lung cancer, colon cancer, prostate cancer, and bladder cancer (Davidson et al, 2010;Song et al, 2010;Tie et al, 2010;Leite et al, 2011;Uesugi et al, 2011;Li et al, 2012a;Li et al, 2012b;Chiyomaru et al, 2012;He et al, 2012). However, the level of miR0218 expression, and its clinical significance in pancreatic cancer, remains to be investigated.…”