Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer

Abstract

Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< rs<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future.

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

“…In addition, forced expression of miR-491-5p inhibited tumor proliferation, disrupted the cell cycle, and induced apoptosis in vitro and in vivo [49]. We also showed that lncRNA RP11-363E7.4 interacted with three miRNAs (miR-17-5p, miR-19b-3p, and miR-106a-5p), which were previously investigated in the reports of Xia et al, Zhang et al, and Qu et al [22,50,51]. …”

EGFR Antibody Conjugated Bimetallic Au@Ag Nanorods for Enhanced SERS-Based Tumor Boundary Identification, Targeted Photoacoustic Imaging and Photothermal Therapy

“…In our previous work, with the aim of finding early gastric cancer, we screen out some new biomarkers associated with early gastric cancer and develop novel ultrasensitive detection methods [8][9]. We also designed and fabricated some multifunctional nanoprobes for targeted imaging and simultaneous therapy of subcutaneous and in situ gastric cancer tissues with 5 mm in diameter [10][11][12][13][14][15][16][17][18][19][20][21][22]. Among those multifunctional nanoprobes, RGDconjugated gold nanorods could target tumor tissues and kill tumor cells via photothermal therapy [14], exhibiting potential clinical application prospects.…”

New Developments of Gastric Cancer Biomarker Research

“…Potential serum microRNA biomarkers included miR-187, miR-371-5p and miR-378, microRNA-21, miR-195, miRNA-206, MiR-16-5p and MiR-19b-3p. Serum miR-187, miR-371-5p and miR-378, microRNA-21, miR-627, miR-629 and miR-652 levels are positively related to gastric cancer while serum miR-195, miRNA-206, MiR-16-5p and MiR-19b-3p levels are negatively correlated with gastric cancer [76][77][78][79][80][81]. miR-378 alone could discriminate GC patients from healthy controls with 87.5% sensitivity and 70.73% specificity.…”