Potential Biomarker For Gastric Cancer Research Articles

Identifying multiple collagen gene family members as potential gastric cancer biomarkers using integrated bioinformatics analysis.

BackgroundGastric cancer is one of the most common malignant cancers worldwide. Despite substantial developments in therapeutic strategies, the five-year survival rate remains low. Therefore, novel biomarkers and therapeutic targets involved in the progression of gastric tumors need to be identified.MethodsWe obtained the mRNA microarray datasets GSE65801, GSE54129 and GSE79973 from the Gene Expression Omnibus database to acquire differentially expressed genes (DEGs). We used the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to analyze DEG pathways and functions, and the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape to obtain the protein–protein interaction (PPI) network. Next, we validated the hub gene expression levels using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA), and conducted stage expression and survival analysis.ResultsFrom the three microarray datasets, we identified nine major hub genes: COL1A1, COL1A2, COL3A1, COL5A2, COL4A1, FN1, COL5A1, COL4A2, and COL6A3.ConclusionOur study identified COL1A1 and COL1A2 as potential gastric cancer prognostic biomarkers.

Potentials of neuron-specific enolase as a biomarker for gastric cancer

Purpose: To investigate the potentials of neuron-specific enolase (NSE) as a biomarker for gastric cancer (GC).
 Methods: Gastric cancer (GC) patients (n = 412) who underwent gastrectomy were recruited over a 3- year period for this study. Their clinicopathological data such as age, sex, histological type, depth, tumor invasion, lymph node metastasis, and distant metastasis were analyzed. The patients were followed up for four years and the outcomes were also assessed. Histological changes in biopsies and levels of expression of NSE in biopsies and serum of patients were determined using immunohistochemical staining, western blotting and enzyme-linked immunosorbent assay (ELISA), respectively.
 Results: Immunohistochemical staining showed that NSE was differentially expressed in the cytoplasm of GC cells. Histological changes in biopsies of patients in the overexpression group were not significantly different from those of patients in under-expression group (p > 0.05). In NSE overexpression group, the number of patients in early stage GC subgroup (n = 186, 86.10 %, T1) were significantly higher than that in advanced GC subgroup (n = 124, 62.20 % T2–T4) (p < 0.05). However, in NSE under-expression group, there were more patients in advanced GC subgroup (n = 72, 37.70 %) than in early GC subgroup (n = 30, 13.80 %) (p < 0.05). Patients in NSE overexpression group survived longer than those in NSE under-expression group (p < 0.05). The level of expression of NSE significantly decreased with increase in TNM stage (p < 0.05). There was no significant difference in serum NSE level between GC patients and healthy control (p > 0.05). The results of the correlation analysis indicated that NSE levels were positively associated with GC.
 Conclusion: The results obtained in this study suggest that NSE could serve as a potential biomarker for GC.
 Keywords: Biomarker, Gastric cancer, Neuron-specific enolase, Overexpression, TNM staging

NME2 Is a Master Suppressor of Apoptosis in Gastric Cancer Cells via Transcriptional Regulation of miR-100 and Other Survival Factors.

Tumorigenesis is a result of uncontrollable cell proliferation which is regulated by a variety of complex factors including miRNAs. The initiation and progression of cancer are always accompanied by the dysregulation of miRNAs. However, the underlying mechanism of miRNA dysregulation in cancers is still largely unknown. Herein we found that miR-100 was inordinately upregulated in the sera of patients with gastric cancer, indicating that miR-100 might emerge as a biomarker for the clinical diagnosis of cancer. The abnormal expression of miR-100 in gastric cancer cells was mediated by a novel transcription factor NME2 (NME/NM23 nucleoside diphosphate kinase 2). Further data revealed that the transcription factor NME2 could promote the transcriptions of antiapoptotic genes including miRNA (i.e., miR-100) and protein-encoding genes (RIPK1, STARD5, and LIMS1) through interacting with RNA polymerase II and RNA polymerase II-associated protein 2 to mediate the phosphorylation of RNA polymerase II C-terminal domain at the 5th serine, leading to the suppression of apoptosis of gastric cancer cells both in vitro and in vivo. In this context, our study revealed that the transcription factor NME2 is a master suppressor for apoptosis of gastric cancer cells. IMPLICATIONS: Our study contributed novel insights into the mechanism involved in the expression regulation of apoptosis-associated genes and provided a potential biomarker of gastric cancer.

Plasma Neurofilament Light Chain May Be a Biomarker for the Inverse Association Between Cancers and Neurodegenerative Diseases.

An inverse association may exist between cancers and neurodegenerative diseases, although convenient biomarkers for verifying this inverse association are lacking. Plasma neurofilament light chain (NfL) is a novel biomarker for neurodegenerative diseases, such as Alzheimer’s disease (AD), but it has not been measured in patients with cancers, such as gastric cancer (GC). We aimed to explore whether plasma NfL could be a biomarker for GC and AD and whether an inverse association of NfL exists between GC and AD. In this study, plasma NfL levels of 60 normal controls (NC), 91 GC subjects, and 74 AD subjects were measured by a highly sensitive single-molecule array assay. We found that GC subjects expressed lower plasma NfL levels but AD subjects expressed higher plasma NfL levels than NCs. After controlling for confounding factors, plasma NfL levels in the GC group were associated with serum tumor marker levels, and plasma NfL levels in the AD group were associated with cognitive performance and cerebrospinal fluid (CSF) pathological marker levels. Across the entire cohort, plasma NfL levels were associated with cognitive performance, CSF pathological marker levels and serum tumor marker levels. These results suggest thatplasma NfL may be a potential biomarker for GC and AD and may be convenient for evaluating the inverse association between cancers and neurodegenerative diseases.

MetaDE-Based Analysis of circRNA Expression Profiles Involved in Gastric Cancer.

Circular RNAs (circRNAs) could play carcinogenic roles in gastric cancer (GC) and have potential to be biomarkers for GC early diagnosis, which needs to be further excavated and supported by more evidence. The study aims to identify more authentic circRNA expression profiles that could function as potential biomarkers in GC. circRNA expression data in three microarrays were downloaded from Gene Expression Omnibus datasets. A systematic meta-analysis based on an integrated dataset pre-processed from the three microarrays was conducted to identify a panel of differentially expressed circRNAs (DEcircs) by using the metaDE package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment were used to note the corresponding functions of DEcircs. Quantitative real-time polymerase chain reaction was applied to verify the DEcircs expression in cancer tissues and adjacent paracancerous tissues. A GC risk-related circRNAs-miRNAs-mRNAs network was further constructed and analyzed. MetaDE analysis suggested 64 DEcircs between cancer tissues and adjacent normal tissues. GO and KEGG analysis showed that the parental genes of these DEcircs were mainly associated with histone methylation, Wnt signalosome and histone methylation activity. Hsa_circ_0005927 and hsa_circ_0067934 were verified in GC tissues, and a GC risk-related network was constructed. MetaDE-based circRNA expression profiles revealed a series of potential biomarkers involved in GC. Two circRNAs, hsa_circ_0005927 and hsa_circ_0067934, could be more authentic biomarkers for GC screening. The GC risk-related network of hsa_circ_0005927/hsa_circ_0067934 and their downstream targets will provide new genetic insights for GC research.

Circulating circRNA Has_Circ_0141633 Serves as a Potential Biomarker for Gastric Cancer

The current study aims to investigate the expression of circRNA has_circ_0141633 in the tissues and serum of patients with gastric cancer (GC). RT-qPCR was used to detect the expression of has_circ_0141633 in the tissues and serum of patients with GC. Pearson's correlation was used to analyze the relationship between the level of serum and tissue has_circ_0141633 in GC patients. Receiver characteristic curve (ROC) was used to evaluate the diagnostic value of the expression of serum has_circ_0141633 in GC patients. The relationship between serum has_circ_0141633 and the clinicopathological characteristic was analyzed in GC patients. Kaplan-Meier method was used to analyze the survival rate. The level of serum and tissue has_circ_0141633 in GC patients was significantly higher than that in controls. Pearson's correlation analysis showed a positive correlation between serum and tissue has_circ_0141633 levels (r = 0.846, p < 0.05). ROC curve analysis showed that the AUC of serum has_circ_0141633 was 0.835 (95% CI: 0.753 - 0.916), with the sensitivity and specificity of 84.5% and 93.6%. The level of serum has_circ_0141633 was significantly increased according to the malignant characteristics of tumor diameter, differentiation, lymph node metastasis, and TNM stage. The median survival time of GC patients with low expression of has_circ_0141633 was longer than that of GC patients with high expression of has_circ_0141633. In summary, upregulation of serum has_circ_0141633 may be expected to be a specific molecular marker for the diagnosis and evaluation of malignant GC.

MicroRNAs as Novel Potential Biomarker in Gastric Cancer: Diagnostic and Prognostic Biomarkers

Abstract

Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance.

Background Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n = 100, p < 0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p = 0.001), TNM stage (p = 0.013), and lymphatic metastasis (p = 0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p = 0.047). Conclusion hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).

Serum Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA Protected by Exosomes as a Potential Biomarker for Gastric Cancer.

BackgroundOur previous research revealed that membrane type 1-matrix metalloproteinase (MT1-MMP) is overexpressed and plays a crucial role in gastric cancer (GC) progression. Exosomes are important for GC carcinogenesis, and the exosomal contents are ideal biomarkers. However, the expression of exosomal MT1-MMP mRNA in serum and its potential significance in GC remains unclear.Material/MethodsThe expression of exosomal MT1-MMP mRNA in serum of patients with GC, chronic gastritis, or atypical hyperplasia, and healthy controls was detected using real-time quantitative RT-PCR. Serum CEA, CA19-9, and CA72-4 were also measured by electrochemiluminescence assay.ResultsExosomes were isolated and identified in serum, and serum exosomal MT1-MMP mRNA was found to be higher in patients with GC compared with healthy controls and patients with chronic gastritis or atypical hyperplasia (all P<0.05). Serum exosomal MT1-MMP mRNA was significantly correlated with tumor diameter, differentiation, Borrmann type, invasion depth, lymphatic metastasis, distal metastasis, and TNM stage. The AUC of exosomal MT1-MMP mRNA was 0.788 (95% CI: 0.714–0.850) with 63.9% sensitivity and 87.1% specificity, and was higher than that of CEA (0.655 (95% CI: 0.573–0.730)). The combination of 2 markers gave an AUC of 0.821 (95% CI: 0.750–0.878), which was better than with the individual marker. The sensitivity, specificity, and positive and negative predictive values were 75.6%, 83.9%, 94.7%, and 47.3%, respectively. Moreover, the multiple logistic regression model showed that tumor diameter, differentiation, invasion depth, and exosomal MT1-MMP mRNA were the risk factors for lymphatic metastasis in GC.ConclusionsOur results characterized serum exosomal MT1-MMP mRNA in GC, providing a foundation for discovering serum exosomes-targeted biomarkers for GC diagnosis.

Overexpression of PURPL and downregulation of NONHSAT062994 as potential biomarkers in gastric cancer

AimsLong non-coding RNAs (LncRNAs) play central roles in the formation and development of gastric cancer (GC). The aim of this study was to evaluate the expression of PURPL and NONHSAT062994 and the relationship between their expressions with clinical characteristics in GC. Main methodsPURPL and NONHSAT062994 LncRNAs and p53 gene expression levels were analyzed both in 50 pairs of cancerous and adjacent noncancerous tissue samples in GC patients using qRT-PCR and in four sets of data obtained from Gene Expression Omnibus (GEO) database. Chi-square (χ2) test was used to determine the relationship between PURPL, NONHSAT062994 RNA levels and the clinicopathological characteristics of GC. Receiver operating characteristic (ROC) curves were drawn to represent sensitivity and specificity of PURPL and NONHSAT062994 expression as markers of GC. Key findingsExpression of PURPL was significantly upregulated in 50 GC samples as well as in GC tissues from GSE13911 and GSE27342 datasets. Our results demonstrated that PURPL RNA level in GC was significantly related to tumor size and histopathological grade. p53 expression at both protein and mRNA levels were significantly decreased in GC tissues compared to adjacent control samples.NONHSAT062994 expression was downregulated in 50-pair GC and GC tissues from GSE13915 dataset. However, NONHSAT062994 showed no consistently differential expression in GSE2637dataset. NONHSAT062994 was significantly associated with histological grade and tumor size. SignificanceOverall, these results suggest that PURPL and NONHSAT062994 may play critical roles in the progression of GC and therefore might be considered as candidate tumor markers for therapeutic goals.

Exosomal MT1-MMP mRNA in Serum As a Potential Biomarker for Gastric Cancer

Background: Our previous results reveal that membrane type 1-matrix metalloproteinase (MT1-MMP) is overexpressed and plays a crucial roles in gastric cancer (GC) progression. Exosomes are important for GC carcinogenesis, and the exosomal contents are used as ideal biomarkers. However, the expression of exosomal MT1-MMP mRNA in serum and its potential significance in GC remains unclear. Methods: The expression of exosomal MT1-MMP mRNA in serum of GC, chronic gastritis, atypical hyperplasia, and healthy controls were detected using real-time quantitative RT-PCR. Meanwhile, serum CEA, CA19-9 and CA72-4 were also measured by electrochemiluminescence assay. Findings: Exosomes were isolated and identified in serum. Our results revealed that exosomal MT1-MMP mRNA in serum was elevated in GC, compared with healthy controls, chronic gastritis, atypical hyperplasia, respectively (all P<0.05). It was significantly correlated with tumor diameter, differentiation, borrmann type, invasion depth, lymphatic metastasis, distal metastasis, TNM stage. AUC of exosomal MT1-MMP mRNA was 0.788 (95%CI: 0.714-0.850) with sensitivity 63.9% and specificity 87.1%, and higher than that of CEA (0.655 (95%CI: 0.573-0.730)). The combination of two markers gave an AUC of 0.821 (95%CI: 0.750-0.878), better than the individual marker. The sensitivity, specificity, positive and negative predictive value were 75.6%, 83.9%, 94.7%, 47.3%, respectively. Moreover, the multiple logistic regression model showed that tumor diameter, differentiation, invasion depth and exosomal MT1-MMP mRNA were the risk factors of lymphatic metastasis in GC. Interpretation: As a pilot investigation to characterizing the serum exosomal MT1-MMP mRNA in GC, our study provided a foundation for discovering serum exosomes-targeted biomarkers for GC diagnosis. Funding Statement: National Natural Science Foundation of China (81572070, 31500741). Natural Science Foundation of Shandong Province (BS2014SW022, ZR2016HM37). Key Research and Development Project of Shandong Province (2016GSF201124, 2015GSF118152). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Our study was approved by Medical Ethics Committee of Qilu Hospital of Shandong University (KYLL-2015-097). The participants signed written informed consents.

PARP1: A potential biomarker for gastric cancer

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide, with an overall 5-y survival rate of 25%. The majority of GCs are caused by infectious agents, including the bacterium Helicobacter pylori (H. pylori) and Epstein–Barr virus (EBV). Furthermore, inappropriate repair of DNA damage can also result in genomic instability, which has shown to be a key factor in carcinogenesis of different regions including gastric region. Present study was designed to explore the association between base excision repair pathway genes, PARP1 and APEX1 and gastric pathology and H. pylori infection. Two hundred gastric cancer tissue samples (114 H. pylori positive and 86 H. pylori negative) and adjacent uninvolved area taken as controls was used for expression analysis of BER pathway genes at mRNA level and protein levels using quantitative PCR (qPCR) and immunohistochemistry (IHC) respectively. Oxidative stress and DNA damage was also determined by measuring the level of antioxidant enzymes and comet assay respectively. Significant upregulation in PARP1 (p < 0.001) and APEX1 (p < 0.02) was observed in GC tissue samples compared to controls and this upregulation was more pronounced in H. pylori positive cases (HPGC) (PARP1, p < 0.02: APEX1, p < 0.04) than H. pylori negative cases (HNGC). Upregulation of BER pathway genes in HPGC was found correlated with smoking status (p < 0.0001), T stage (p < 0.01) and lymph node metastasis (p < 0.03). Moreover, immunohistochemical staining of BER pathway genes was found correlated with a number of clinicopathological characteristics such as tumor type (p < 0.03), tumor size (p < 0.01) and lymph node metastasis (p < 0.01). Expression levels of APEX1 and PARP1 gene also correlated with increased oxidative burden (p < 0.0001) and DNA damage (p < 0.001) in GC patients. Survival analysis showed that upregulation of PARP1 gene was associated with poor overall survival outcome of gastric cancer patients (HR = 2.04 (95% CI = 1.10–3.76; p < 0.02). Univariate and multivariate cox regression analysis showed the upregulated PARP1 gene (HR = 5.03; 95%CI (2.22–11.35); p = 0.0001), positive smoking status (HR = 3.58; 95%CI (1.67–7.65); p = 0.001), positive status for H pylori infection (HR = 4.38; 95%CI (1.82–10.56); p = 0.001) and advance N-stage (HR = 5.29; 95%CI (2.28–12.24); p = 0.0001) were independent prognostic factors for gastric cancer and may serve as a valuable biomarker for the diagnosis and progression of GC and can be helpful in developing individualized treatment strategies for treating GC.

Identification of plasma RGS18 and PPBP mRNAs as potential biomarkers for gastric cancer using transcriptome arrays.

Coding and noncoding RNAs serve a crucial role in tumorigenesis. Circulating RNAs have been recognized as a novel category of biomarkers for a variety of physiological and pathological conditions. To identify plasma RNA biomarkers for gastric cancer (GC), a genome-wide transcriptome analysis using GeneChip® Human Transcriptome Array, which contains probe sets covering exons of ~67500 coding and noncoding transcripts of annotated genes, was performed to screen for the RNAs that exhibited differential expression in the plasma samples of patients with GC and controls. The expression levels of 6 candidate RNAs, including regulator of G-protein signaling 18 (RGS18), integral membrane protein 2B, pro-platelet basic protein (PPBP), nucleosome assembly protein1-like 1, n324674 and ENST00000442382 were assessed in the plasma samples of 81 patients with GC and 77 healthy participants using reverse transcription-quantitative polymerase chain reaction. Furthermore, the expression levels of RGS18 and PPBP mRNAs were indicated to be significantly differentially expressed (P<0.0001) in an independent panel of plasma samples of 36 patients with GC compared with 34 healthy participants. The potential association of RGS18 and PPBP mRNA expression levels with clinicopathological features was subsequently analyzed. Receiver operating characteristic analysis indicated that the combination of these 2 mRNAs with an area under curve <0.812 was an improved indicator for gastric cancer compared with respective individual levels. The results of the present study indicate that RGS18 and PPBP mRNA expression was significantly downregulated in the plasma of patients with GC, and the combination of these 2 mRNAs may be a useful diagnostic or prognostic marker for GC.

Prognostic value of gastric cancer‐associated gene signatures: Evidence based on a meta‐analysis using integrated bioinformatics methods

Selecting differentially expressed genes (DEGs) based on integrated bioinformatics analyses has been used in previous studies to explore potential biomarkers in gastric cancer (GC) with microarray and RNA sequencing data. However, the genes obtained may be inaccurate because of noisy data and errors, as well as insufficient clinical sample sizes. Thus, we aimed to find robust and strong DEGs with prognostic value for GC, where the robust rank aggregation method was employed to select significant DEGs from eight Gene Expression Omnibus data sets with a total of 140 up‐regulated and 206 down‐regulated genes. Network data mining was then used to screen hub genes, and 11 genes were filtered using Fisher's exact test. Based on these results, we built a prognostic signature with seven genes (FBN1,MMP1,PLAU,SPARC,COL1A2,COL2A1 and ATP4A) using stepwise multivariate Cox proportional hazard regression. According to the risk score for each patient, we found that high‐risk group patients had significantly worse survival results compared with those in the low‐risk group (log‐rank test P‐value < 0.001). This seven‐gene signature was then validated with an external data set. Thus, we established a signature based on seven DEGs with prognostic value for GC patients using multi‐steps bioinformatics methods, which may provide novel insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.

Plasma long non-coding RNA HOTAIR as a potential biomarker for gastric cancer.

Long non-coding RNAs (lncRNAs) Hox transcript antisense intergenic RNA ( HOTAIR) has been suggested to be implicated in gastric cancer tumorigenesis and progression; however, little is known about the role of the plasma HOTAIR in gastric cancer diagnosis and prognosis. The current study was aimed at investigating the clinical relevance of plasma long non-coding HOTAIR as a non-invasive diagnostic biomarker in gastric cancer. Plasma HOTAIR expression was measured in 50 patients with newly diagnosed gastric cancer and 50 age- and sex-matched healthy controls using quantitative reverse transcription polymerase chain reaction. Plasma level of HOTAIR was significantly higher in gastric cancer patients compared with healthy controls ( P < 0.001). By using receiver operating characteristic curve analysis, it was found that plasma HOTAIR could diagnose gastric cancer with 88% sensitivity and 84% specificity. Furthermore, increased HOTAIR expression was associated with advanced tumor stages, higher grades, and metastasis. Plasma HOTAIR might serve as a potential non-invasive biomarker for diagnosis of gastric cancer.

LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer.

DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction. Significant hypomethylation of LINE-1 and overexpression of UHRF1 were observed in GC tissues compared with the matched controls (P<0.001 and P=0.001, respectively). LINE-1 hypomethylation was inversely correlated with UHRF1 overexpression in GC tissues (r=-0.026, P=0.028). In addition, LINE-1 hypomethylation in GC was significantly associated with Lauren's histological classification, tumor differentiation and background intestinal metaplasia (P=0.014, P=0.042 and P=0.034, respectively). These results suggest that LINE-1 hypomethylation may be a potential biomarker for GC and it is indirectly regulated by UHRF1 overexpression.

Diagnostic Value of MicroRNA-18a for Gastric Cancer: a Meta-Analysis.

Emerging data demonstrated that circulating microRNA-18a (miR-18a) expression level was significantly different between gastric carcinoma individuals and healthy groups, implying that miR-18a may be a potential biomarker for gastric cancer. Nevertheless, the reports remain inconsistent. This meta-analysis was performed to evaluate the diagnostic value of miR-18a in gastric tumor detection. All the relevant papers were searched and collected until July 2017 in PubMed, Cochrane Library, Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wanfang Database. Data was extracted from eligible studies. Diagnostic performance of miR-18a for gastric cancer were evaluated using STATA (version 12.0) and MetaDisc (version 1.4) statistical software. Three studies were included in this meta-analysis with a total of 235 gastric cancer patients and 136 controls enrolled. The pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circulating miR-18a to discriminate GC patients were 0.76 (95% confidence interval CI: 0.70, 0.81), 0.73 (95% CI: 0.65, 0.80), 2.76 (95% CI: 2.08, 3.65), 0.32 (95% CI: 0.19, 0.55), and 9.12 (95% CI: 4.36, 19.09), respectively. The area under the summary receiver operator characteristic (SROC) curve was 0.82. miR-18a could be a promising noninvasive biomarker in gastric carcinoma diagnosis. Further prospective studies should be conducted to highlight the theoretical strengths before its use in clinic.

Long noncoding RNA LINC00978 promotes cancer growth and acts as a diagnostic biomarker in gastric cancer.

Long noncoding RNAs (lncRNAs) play important roles in cancer development and progression. The deregulated expression of LINC00978 has been reported in human cancers. However, the expression pattern and biological roles of LINC00978 in gastric cancer (GC) remain unclear. In this study, we investigated the potential roles and clinical value of LINC00978 in gastric cancer. QRT-PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines, tissues and serum samples. Cell counting, colony formation, transwell migration and matrigel invasion assays were performed to determine the effects of shRNA-mediated knockdown of LINC00978 on gastric cancer cell functions. In vivo tumour growth assay was also conducted. Flow cytometry, immunohistochemistry, western blot and qRT-PCR were used for potential mechanism study. LINC00978 expression level was elevated in GC tumour tissues, serum samples and cell lines. The expression level of LINC00978 was significantly correlated with tumour size (P=0.02), lymphatic metastasis (P=0.009) and TNM stage (P=0.009). LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis. LINC00978 knockdown also inhibited the migration and invasion of GC cells. In addition, LINC00978 knockdown inhibited the activation of TGF-β/SMAD signalling pathway and the process of epithelial-mesenchymal transition (EMT) in GC cells. Moreover, the in vivo tumorigenicity of LINC00978 knockdown GC cells in mice was significantly decreased. LINC00978 promotes gastric cancer progression and may serve as a potential biomarker for GC.

Serum microRNA panel excavated by machine learning as a potential biomarker for the detection of gastric cancer.

Early detection of gastric cancer (GC) is crucial to improve the therapeutic effect and prolong the survival of patients. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs that function as repressors of diverse genes. We aimed to identify a microRNA panel in the serum of patients to predict GC non-invasively with high accuracy and sensitivity. Using six types of classifiers, we selected three markers (miR‑21-5p, miR-22-3p and miR-29c-3p) from a published miRNA profiling study (GSE23739) which was treated as a training set. The values of the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.9437, 0.9456 and 0.9563 in the three classifiers [Compound covariate classifier, Diagonal linear discriminant analysis (DLDA) classifier and Support vector machine classifier], respectively. Then the panel was validated further in another two miRNA profiles in GEO (Gene Expression Omnibus) databases (GSE26595, GSE28700) with high AUC values as well. Next, we found that the serum levels of miR-21 were significantly higher in GC patients than levels in healthy controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for confirmation, which was opposite to the serum levels of miR-22 and miR-29c (all P<0.0001). Finally, using bioinformatic tools, their biological mechanisms were elucidated by their predicted targets: Sp1 (miR-21) and PTEN (miR-22 and miR-29c). This miRNA panel is a non‑invasive and potential biomarker for GC.

Downregulated expression of hsa_circ_0074362 in gastric cancer and its potential diagnostic values.

To explore the diagnostic value of hsa_circ_0074362 in the screening of gastric cancer. The expression levels of hsa_circ_0074362 in 127 gastric cancer tissues and paired adjacent normal tissues, 83 gastritis tissues and six gastric cancer cell lines were first detected by quantitative reverse transcription-polymerase chain reaction. Then, the relationship between its levels and clinicopathological factors of patients with gastric cancer was analyzed. Finally, a receiver operating characteristic curve was established. Hsa_circ_0074362 levels were significantly downregulated in gastric cancer tissues, gastritis tissues and gastric cancer cell lines. Its levels were associated with lymphatic metastasis. Hsa_circ_0074362 probably plays a role in the initiation of gastric cancer and may be a potential biomarker of gastric cancer.