Long intergenic non-protein-coding RNA 152 (LINC00152) is one of the long noncoding RNAs (lncRNAs) abnormally expressed in gastric cancer tissues. However, its value in the diagnosis of gastric cancer is unclear. The aim of this study is to evaluate the clinical significance of plasma LINC00152 as a biomarker in the screening of gastric cancer and to explore the possible mechanism underling its stable existence in blood. We analyzed the levels of plasma LINC00152 in patients with gastric cancer and gastric epithelial dysplasia and healthy controls using quantitative reverse transcription polymerase chain reaction and then confirmed by sequencing. We also compared its levels in paired preoperative and postoperative plasma samples. In addition, we compared the levels of LINC00152 in plasma and in exosomes, which were extracted from the same plasma and confirmed by transmission electron microscopy. The levels of plasma LINC00152 were significantly elevated in gastric cancer patients compared with healthy controls. The sensitivity and specificity of plasma LINC00152 in the diagnosis of gastric cancer were 48.1 and 85.2%, respectively. There were no significant differences of LINC00152 levels between gastric epithelial dysplasia patients and healthy controls. LINC00152 levels in preoperative plasma samples were lower than those in postoperative ones. There were also no differences between LINC00152 levels in plasma and in exosomes. All these results suggested that LINC00152 can be detected in plasma, and one of the possible mechanisms of its stable existence in blood was protected by exosomes. It has the possibility to be applied in gastric cancer diagnosis as a novel blood-based biomarker.

BACKGROUND: MicroRNAs (miRNAs) play a crucial role in carcinogenesis; however, it largely remains unclear whether miRNAs in gastric juice, which is specific for gastric tissues, can be used as biomarkers for gastric cancer. The objective of the current study was to investigate the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer. METHODS: Gastric juice samples were collected from 141 patients who underwent upper gastrointestinal endoscopy examination between September 2010 and December 2011. Gastric cancer and adjacent normal biopsy specimens also were collected. The existence and stability of miRNAs in gastric juices were determined by real-time reverse transcriptase-quantitative polymerase chain reaction (RTqPCR) and sequencing. miRNA levels in tissues and gastric juices were detected by RT-qPCR. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases. RESULTS: Levels of miRNA-21 (miR-21) and miR-106a in gastric cancer tissues were significantly higher compared with the levels in adjacent tissues (P ¼ .006 and P ¼ .001, respectively). Patients who had gastric cancer had significantly different levels of gastric juice miR-21 and miR-106a compared with patients who had benign gastric diseases (both P < .001). There were significant correlations between miR-21/miR-106a levels and Borrmann types. miR-21 levels in intestinal type gastric cancer specimens were higher than that in diffuse (P ¼ .003) or mixed (P < .001) gastric cancer types. The area under the ROC curve was up to 0.969 for miR-21 and 0.871 for miR-106a. CONCLUSIONS:The current results indicated that certain miRNAs in gastric juice are potential biomarkers that can assist in screening for gastric cancer.

MicroRNA-421 (miR-421) plays crucial roles during carcinogenesis and is a potential tumor marker in the diagnosis of several types of cancers. However, whether miR-421 in gastric juice, which is specific for gastric tissue, can be used as a biomarker for gastric cancer screening is unclear. In the present study, real-time quantitative reverse transcription-polymerase chain reaction was used to analyze miR-421 levels in gastric juice from patients with gastric cancer or benign gastric disease, or normal. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. The results showed that gastric juice levels of miR-421 in patients with gastric cancer were significantly different from those in benign gastric diseases (P < 0.001). The area under the ROC curve of miR-421 was up to 0.767 (95 % CI = 0.684-0.850). The levels of miR-421 in gastric juice from gastric patients were not significantly associated with the main clinicopathological factors such as tumor size, Lauren's classification, and Borrmann's classification. For the detection of early gastric cancer, the use of gastric juice miR-421 showed a remarkable improvement compared with the use of serum carcinoembryonic antigen alone. These results indicated that gastric juice miRNAs such as miR-421 are useful biomarkers for screening gastric cancer.

Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A (p16), E-cadherin (CDH1), runt-related transcription factor 3 (RUNX3), human mutL homolog 1 (MLH1), RAS association domain family protein 1A (RASSF1A), cyclin-dependent kinase inhibitor 2B (p15), adenomatous polyposis coli (APC), Glutathione S-transferase P1 (GSTP1), TP53 dependent G2 arrest mediator candidate (Reprimo), and O6-methylguanine-DNAmethyl-transferase (MGMT) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls. While death-associated protein kinase (DAPK) promoter methylation was not correlated with GC. Further analyses demonstrated that RUNX3, RASSF1A and Reprimo promoter methylation had a good diagnostic capacity in blood samples of GC versus non-tumor controls (RUNX3: sensitivity = 63.2% and specificity = 97.5%, RASSF1A: sensitivity = 61.5% and specificity = 96.3%, Reprimo: sensitivity = 82.0% and specificity = 89.0%). Our findings indicate that promoter methylation of the RUNX3, RASSF1A and Reprimo genes could be powerful and potential noninvasive biomarkers for the detection and diagnosis of GC in blood samples in clinical practices, especially Reprimo gene. Further well-designed (multi-center) and prospective clinical studies with large populations are needed to confirm these findings in the future.

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