The Identification of miR-375 as a Potential Biomarker in Distal Gastric Adenocarcinoma

Abstract

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level and play an important role in carcinogenesis. Herein, we characterized the global expression of miRNA in distal gastric adenocarcinomas and determined if circulating miRNAs could be used as biomarkers for distal gastric adenocarcinoma. We used a microarray screening system to detect dysregulated miRNAs in distal gastric adenocarcinoma tissues. The expression of a subset of five aberrantly expressed miRNAs (miR-375, -196b, -204, -18b, and -93) were further quantified in an independent set of clinical samples of distal gastric adenocarcinoma by real-time quantitative RT-PCR (rt-qRT-PCR). We also used rt-qRT-PCR to investigate the expression levels of putative miRNA biomarkers in serum and tumor cell lines. In our study, the expression of a subset of microRNAs was altered in distal gastric adenocarcinoma compared to normal tissue, miR-375 was significantly downregulated in distal gastric adenocarcinoma tissues, to a level that was significantly lower than cardia adenocarcinoma (p < 0.05). The circulating serum levels of miR-375 in patients who had distal gastric adenocarcinoma were also much lower than normal controls (p < 0.001). As a biomarker, miR-375 yielded a receiver operating characteristic area under the curve of 0.835. The specificity and sensitivity was 80% and 85%, respectively, in the discrimination of distal gastric adenocarcinoma from control, at a normalized cutoff of 0.218. The expression of miR-375 was downregulated both in distal gastric adenocarcinoma tissues and serum of patients with distal gastric adenocarcinoma. These data suggest miR-375 is a potential biomarker for distal gastric adenocarcinoma.

Circulating microRNAs: potential biomarkers for common malignancies

“…Another potential prognostic biomarker is miR-375, with low expression in sera associated with poorer overall survival rates [117]. Interestingly, the study by Zhang et al [118] analyzed plasma miRNA levels in combination with mutations in the EGFR. These mutations in EGFR are often observed in female patients with adenocarcinomas and no prior history of smoking.…”

MicroRNA-10b inhibits proliferation, migration and invasion in cervical cancer cells via direct targeting of insulin-like growth factor-1 receptor

“…miRNAs regulate the activity of >30% of human genes, and therefore perform important roles in a variety of physiological and pathological processes, including cell proliferation, apoptosis, metastasis, glucose and lipid metabolism, and infection and immune responses (16)(17)(18)(19)(20). Previous studies have demonstrated that miRNAs are deregulated in numerous types of human cancers, and are associated with tumorigenesis and development by regulation of oncogenes or tumor suppressors (21)(22)(23).…”

Altered MiRNA Expression in Gastric Cancer: a Systematic Review and Meta-Analysis

“…Although we found hundreds of altered miRNAs, only members from the miR-17-92 cluster and its two paralogues were consistently upregulated [12,13,14,15,16,17,18,19,22,23,25,26,27]. We have also summarized miRNAs that were up-regulated in at least 4 of the 19 studies and down-regulated in at least 3 studies in Table 2.…”

“…As for the feasibility to obtain blood sample, almost all studies recruited healthy individual as a normal control except Zhang et al [34] who recruited normal mucosa or minimal gastritis in 99 patients as a control. In addition, Li et al [30] focused on early stages of gastric cancer and Zhang et al [18] focused on serum in distal gastric adenocarcinomas compared with 20 age-matched healthy individuals.…”

“…Three studies [10,12,27] did not provide data on miRNA fold changes while in all other studies, a 1.5 fold change was used to pick up-regulated or down-regulated miRNAs. Histopathological grading information was provided in seven [12,13,16,18,19,24,26] studies.…”