Dataset Information

Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis.

ABSTRACT: Background:Long non-coding RNAs (lncRNAs) participate in a series of pathological processes in tumorigenesis. Reports show that C5orf66-AS1, an antisense lncRNA, is expressed in various tumors. However, the role of C5orf66-AS1 in gastric cancer (GC) has not been fully clarified. The study focused on the expression patterns and serum level of C5orf66-AS1 in GC to explore its potential application in GC screening and diagnosis. The effects of C5orf66-AS1 on GC cells were also analyzed. Methods:Tissue and serum samples were used for RNA isolation. Expression levels of C5orf66-AS1 in GC tissues, serum, and cell lines were detected using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). CCK-8, transwell, and wound healing assays were performed to determine the effects of C5orf66-AS1 on GC cell behavior. Results:C5orf66-AS1 expression was downregulated in GC cells compared to that in adjacent normal tissues. Serum C5orf66-AS1 levels were significantly lower in GC patients than in superficial gastritis (GS) and atrophic gastritis (GA) patients. Low serum expression of C5orf66-AS1 was associated with an increased risk of gastric dysplasia (GD) and GC. Receiver operating characteristic curve results showed that the area under curve (AUC) for GC was 0.688, with a sensitivity and specificity of 77.5% and 53.6%, respectively. For the GD + early gastric cancer (ECG) group, the AUC was 0.789, with a sensitivity and specificity of 85.15% and 62.86%, respectively. Correlation analyses of clinicopathological parameters showed that serum C5orf66-AS1 was predominantly associated with Lauren type, TNM stages, pTNM stages, and vessel tumor emboli. Additionally, in vitro overexpression of C5orf66-AS1 in AGS cells inhibited cell proliferation, migration, and invasion. Conclusion:Decreased expression levels of serum C5orf66-AS1 can be utilized for diagnosis of GC, especially for early diagnosis. The low level of serum C5orf66-AS1 indicated poor biological behavior of tumors in GC patients. In addition, C5orf66-AS1 can inhibit GC cell proliferation, migration, and invasion.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC7136487 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis.

Zhou Quan Q Li Hao H Jing Jingjing J Yuan Yuan Y Sun Liping L

OncoTargets and therapy 20200402

<h4>Background</h4>Long non-coding RNAs (lncRNAs) participate in a series of pathological processes in tumorigenesis. Reports show that C5orf66-AS1, an antisense lncRNA, is expressed in various tumors. However, the role of C5orf66-AS1 in gastric cancer (GC) has not been fully clarified. The study focused on the expression patterns and serum level of C5orf66-AS1 in GC to explore its potential application in GC screening and diagnosis. The effects of C5orf66-AS1 on GC cells were also analyzed.<h4> ...[more]

PMID: 32308414

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Project description:ObjectiveMicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC).Materials & methodsThe miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed.ResultsElevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC.ConclusionsOverexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.

Project description:Previous studies proved that long noncoding RNAs (lncRNAs) play important role in human cancer. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Next generation RNA sequencing (RNA-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer (DGC) patients. Then we performed a comprehensive analysis on lncRNAs and mRNA. Fifty-eight lncRNAs were upregulated and 54 lncRNAs were downregulated in diffuse gastric cancer tissue compared with adjacent tissue. The numbers of up- and downregulated mRNAs were 306 and 161, respectively. In addition, we inferred the function of lncRNAs by construction of a co-expression network for deregulated mRNAs and lncRNAs. Co-expressed genes of MEF2C-AS1 and FENDRR were enriched to RAS and TGF-beta signaling pathway. MEF2C-AS1 and FENDRR expression were re-evaluated by Real-time Quantitative PCR in 42 DGC patients' tumor and normal tissues, and other 46 DGC patents' and 21 healthy controls' plasma. Validation data showed MEF2C-AS1 and FENDRR were significantly downregulated in tumor tissues compared with normal tissues. And decreased FENDRR are associated with aggressive tumor characteristics including more advanced stage (P = .030), poor differentiation (P = .043) and lymphatic metastasis (P = .001). The expression level MEF2C-AS1 was significantly lower in DGC patients' plasma than that in healthy controls' plasma. In gastric cancer cell lines, knock-down of MEF2C-AS1 or FENDRR reduced the protein levels of FAT3, NTN1 and LYVE1 (the co-expressed genes), which were related with gastric cancer cell proliferation and invasion by previous studies. In addition, knock-down of MEF2C-AS1 or FENDRR promoted aggressive tumor behaviors in in-vitro assays. In this study, we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.

Dataset Information

Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis.

Publications

Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis.

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