Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17+ γδT cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related γ and δ variable γδTCR chains (Vγ1, Vγ2, Vγ3, Vδ4, and Vδ6.3), observing that maternal OVA-immunization inhibits Vγ2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing γδT cells possibly by an epigenetic mechanism mediated by miRNAs.

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miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽

10.3390/genes9110545 ◽

2018 ◽

Vol 9 (11) ◽

pp. 545 ◽

Cited By ~ 5

Author(s):

Wei Wu ◽

Lingxiang Wu ◽

Mengyan Zhu ◽

Ziyu Wang ◽

Min Wu ◽

...

Keyword(s):

Somatic Mutations ◽

Target Genes ◽

Expression Profiles ◽

Tumor Development ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Messenger Rnas ◽

Cellular Functions ◽

Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

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Identification of potential key genes in anaplastic thyroid cancer using bioinformatics analysis

10.21203/rs.3.rs-378231/v1 ◽

2021 ◽

Author(s):

Zhenzhen Li ◽

Xiong Chaoliang ◽

Jin Wei ◽

Ping Chen ◽

Yanping Zhang ◽

...

Keyword(s):

Survival Analysis ◽

Thyroid Cancer ◽

Target Genes ◽

Collagen Type ◽

Expression Profiles ◽

Thyroid Tissue ◽

Anaplastic Thyroid Cancer ◽

Type I ◽

Tissue Samples ◽

Km Plotter

Abstract Background Anaplastic thyroid cancer (ATC) has a high degree of malignancy and a poor prognosis. Its incidence accounts for approximately 10–15% of all thyroid cancers. The purpose of this study was to determine the differentially expressed genes (DEGs) of ATC through biometric analysis technology, clarify the potential interactions between them, and screen genes related to the prognosis of ATC. Methods The GSE29265, GSE65144, GSE33630, and GSE85457 expression profiles downloaded from the Gene Expression Omnibus database (GEO) contained a total of 117 tissue samples (81 normal thyroid tissue samples and 36 ATC samples). The four datasets were integrated and analyzed by the limma packages to obtain DEGs. With these DEGs, we performed gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses using the Database for Annotation, Visualization and Integrated Discovery, protein-protein interaction (PPI) analysis using Cytoscape, and survival analysis using the Kaplan-Meier (KM) plotter. Results. After R integration analysis of the four datasets, 764 DEGs were obtained, i.e., 314 upregulated and 450 downregulated genes. Among the hub DEGs obtained in the PPI network, the expression levels of thymidylate synthase (TYMS), fibronectin 1, chordin-like 1, syndecan 2, integrin alpha 2, collagen type I alpha 1 chain, collagen type IX alpha 3 chain (COL9A3), and collagen type XXIII alpha 1 chain (COL23A1) were associated with ATC prognosis. These results showed that the overall survival and recurrence-free survival of TYMS, COL9A3, and COL23A1 were statistically significant in our KM plotter survival analysis; thus, these DEGs may be used as potential biomarkers of ATC. Conclusion This study identified several potential target genes and pathways that may affect the development of ATC. These findings provide new insights for the detection of novel diagnostic and therapeutic biomarkers for ATC.

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Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.780621 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhaoyi Lu ◽

Kai Su ◽

Xiaomin Wang ◽

Mingjie Zhang ◽

Shiyin Ma ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Small Rnas ◽

Target Genes ◽

Expression Profiles ◽

Target Prediction ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Diagnostic Efficiency ◽

Sequencing Data ◽

Qrt Pcr

Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown.Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC’s pathogenesis.Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC.Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.

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Integrated analysis of lncRNA-miRNA-mRNA ceRNA network and the potential prognosis indicators in sarcomas

10.21203/rs.3.rs-21667/v1 ◽

2020 ◽

Author(s):

Ling Zhang ◽

Lu Gao ◽

Yu Zhao ◽

Xuelei Ma

Keyword(s):

Survival Analysis ◽

Protein Interactions ◽

Sequence Data ◽

Gene Prediction ◽

Expression Profiles ◽

Enrichment Analysis ◽

Integrated Analysis ◽

Pathway Enrichment Analysis ◽

Tissue Samples ◽

Cerna Network

Abstract The ceRNA network has been demonstrated to play crucial roles in multiple biological processes and the development of neoplasms, which have the potential to become diagnostic and prognosis markers and therapeutic targets. In this work, we comparing the expression profiles between sarcoma identified differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) in sarcomas and normal tissue samples in GEO datasets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to investigate the major functions of the overlapping DEGs. Then, lncRNA-miRNA interactions and miRNA-mRNA interactions were predicted, and a ceRNA regulatory network was constructed. In addition, the mRNAs included in ceRNA network were used to construct the protein-protein interactions network, and the survival analysis of sarcomas was performed according to the biomarkers included in the ceRNA network. According to the RNA sequence data from GEO dataset, 1296 DEGs were identified in sarcoma samples by combining the GO and Pathway enrichment analysis, 338 DELs were discovered after re-annotating the probes, and 36 DEGs were ascertained through intersecting two different expression miRNAs sets. Further, 448 miRNA-mRNA interactions and 454 miRNA-lncRNA interactions were obtained through target gene prediction, and then, we constructed a lncRNA-miRNA-mRNA ceRNA network containing 9 miRNAs, 69 lncRNAs and 113 mRNAs. PPI network showed that the hub up-regulated nodes include IGF1, PRKCB and GNAI3, and the hub down-regulated nodes include AR, CYCS and PPP1CB. Survival analysis revealed that the expression levels of 12 RNAs involved in the ceRNA network were associated with overall survival of sarcoma patients. Our study showed that the ceRNA network in sarcomas based on that lncRNA could serve as ceRNA and discovered the potential indicators for prognosis of sarcoma patients.

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An Integrated Analysis of mRNAs and miRNAs Microarray Profiles to Screen miRNA Signatures Involved in Nasopharyngeal Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820956998 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095699

Author(s):

Lei Liu ◽

Hailing Wang ◽

Chaohui Yan ◽

Shudong Tao

Keyword(s):

Nasopharyngeal Carcinoma ◽

Target Genes ◽

Expression Profiles ◽

Area Under The Curve ◽

Gene Expression Omnibus ◽

Integrated Analysis ◽

Messenger Rnas ◽

Screening Criteria ◽

Go Annotation ◽

Microarray Datasets

Objective: We aim to identify several microRNAs (miRNAs/miRs)-messenger RNAs (mRNAs) biomarkers correlated to nasopharyngeal carcinoma (NPC) based on an integrated analysis of miRNA and mRNAs microarray expression profiles. Methods: The available mRNA and miRNA microarray datasets were retrieved from Gene Expression Omnibus (GEO) database according to pre-determined screening criteria. Differentially expressed miRNA and mRNAs (DEmiRNAs and DEmRNAs) were extracted between NPC and noncancerous nasopharyngeal tissues. The target genes of DEmiRNAs were predicted with miRTarBase followed by the construction of DEmiRNAs-target DEmRNAs network, and functional analyses were performed. The DEmiRNAs expressions were validated and the performance of these DEmiRNAs was assessed by the area under the curve (AUC) values. Finally, the correlations between DEmiRNAs and specific clinical factors were analyzed. Results: There were 1140 interaction pairs (including let-7d/f- MYC/ HMGA2 and miR-452- ITGA9) in DEmiRNAs-target DEmRNAs network. The GO annotation analysis showed that several genes such as MYC, HMGA2 and ITGA9 primarily participated in cellular process. KEGG analysis showed that these targets were associated with cell cycle and cancer-related pathways. Down-regulated let-7(-d and –f) and up-regulated miR-452 were verified in datasets. The AUC values of these 3 DEmiRNAs (let-7d, let-7-f and miR-452) was 0.803, 0.835 and 0.735, respectively. Besides, miR-452 was significantly related to survival rate of NPC patients. Conclusion: The findings implied let-7d/f- MYC/ HMGA2 and miR-452- ITGA9 might be promising targets for the detection and treatment of NPC.

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SMRT sequencing of the full-length transcriptome of Odontotermes formosanus (Shiraki) under Serratia marcescens treatment

Scientific Reports ◽

10.1038/s41598-020-73075-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kai Feng ◽

Xiaoyu Lu ◽

Jian Luo ◽

Fang Tang

Keyword(s):

Protein Kinase ◽

Serratia Marcescens ◽

Target Genes ◽

Mapk Pathway ◽

Full Length ◽

Mitogen Activated Protein Kinase ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Sequencing Platform ◽

Odontotermes Formosanus

Abstract Odontotermes formosanus (Shiraki) is an important pest in the world. Serratia marcescens have a high lethal effect on O. formosanus, but the specific insecticidal mechanisms of S. marcescens on O. formosanus are unclear, and the immune responses of O. formosanus to S. marcescens have not been clarified. At present, genetic database resources of O. formosanus are extremely scarce. Therefore, using O. formosanus workers infected by S. marcescens and the control as experimental materials, a full-length transcriptome was sequenced using the PacBio Sequel sequencing platform. A total of 10,364 isoforms were obtained as the final transcriptome. The unigenes were further annotated with the Nr, Swiss-Prot, EuKaryotic Orthologous Groups (KOG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Ortholog public databases. In a comparison between the control group and a Serratia marcescens-infected group, a total of 259 differentially expressed genes (DEGs) were identified, including 132 upregulated and 127 downregulated genes. Pathway enrichment analysis indicated that the expression of the mitogen-activated protein kinase (MAPK) pathway, oxidative stress genes and the AMP-activated protein kinase (AMPK) pathway in O. formosanus may be associated with S. marcescens treatment. This research intensively studied O. formosanus at the high-throughput full-length transcriptome level, laying a foundation for further development of molecular markers and mining of target genes in this species and thereby promoting the biological control of O. formosanus. Furthermore, these results will be helpful to clarify the action mechanisms of S. marcescens on O. formosanus, and also explore the relationship between O. formosanus and S. marcescens. In addition, this study will identify the immune response of O. formosanus to S. marcescens, which will provide a theoretical foundation for the development of new immunosuppressants for O. formosanus.

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An Integrative Data Mining for the Identification and Validation of Oncogenic Biomarkers in Pancreatic Carcinoma

10.21203/rs.3.rs-40998/v1 ◽

2020 ◽

Author(s):

Guihua Jin ◽

Qingqing Ruan ◽

Fugen Shangguan ◽

Linhua Lan

Keyword(s):

Early Diagnosis ◽

Western Blot ◽

Pancreatic Carcinoma ◽

Target Genes ◽

Expression Profiles ◽

Human Tumor ◽

Differentially Expressed ◽

Ductal Adenocarcinoma ◽

Pathway Enrichment Analysis ◽

Diagnosis And Therapy

Abstract Background: Pancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy made great progress, outcomes of pancreatic ductal adenocarcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets to improve outcomes of patients. Methods: To identify general applicable targets for early diagnosis and therapy, we selected related microarray data which including three mRNA microarray datasets GSE62165, GSE15471, GSE32676 and two miRNA datasets GSE24279, GSE32678, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using the DAVID database. MiRTarBase, miRWalk, Diana Tools and TBtools were used to get keys. TCGA database, HPA database and western blot experiments were used to verify diagnostic and prognostic value of key genes.Results: By integrating mRNA and miRNA expression profiles, we identified 114 differentially expressed genes (DEGs) and 114 differentially expressed miRNAs (DEMs), respectively. Furthermore, three overlapping key genes, RUNX2, LAMC2 and FBXO32, were found by compared with DEMs target genes and DEGs. In detail, deregulation of 8 key miRNAs were closely related to poor outcomes and participated in crucial genes regulation which may contribute to build a miRNA biomarker panel for prognosis. Moreover, we confirmed that RUNX2 showed a potential property for distinguishing PC and normal people. We also demonstrated that aberrant over-expression of LAMC2 was associated with poor prognosis of PC patients as well as human tumor status and subtypes. The protein levels of RUNX2 and LAMC2 in PC patients were further verified by IHC from Human Protein Atlas and western blot experiments. Conclusions: In summary, our current study identified that RUNX2 and LAMC2 may be promising targets for early diagnosis and therapy of PC patients.

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Investigation of microRNA Expression Profiles Associated with Human Alcoholic Cardiomyopathy

Cardiology ◽

10.1159/000370028 ◽

2015 ◽

Vol 130 (4) ◽

pp. 223-233 ◽

Cited By ~ 15

Author(s):

Ling Jing ◽

Chengmei Jin ◽

Ying Lu ◽

Pingyan Huo ◽

Lijun Zhou ◽

...

Keyword(s):

Real Time ◽

Target Genes ◽

Inositol Phosphate ◽

Expression Profiles ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Rt Pcr ◽

Alcoholic Cardiomyopathy ◽

Differentially Expressed Mirnas ◽

Human Alcoholic

Objectives: We aimed to investigate the differentially expressed microRNAs (miRNAs) and their target genes in human alcoholic cardiomyopathy (ACM). Methods: The expression levels of plasma miRNAs of 78 male ACM patients and 78 healthy men were detected by using the 6th-generation miRCURY™ LNA array (v.16.0). The prediction analysis for microarrays (PAM) method was used to identify the differentially expressed miRNAs. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 5.2 and Miranda. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to perform functional annotation and pathway enrichment analysis of target genes respectively, followed by real-time RT-PCR analysis to validate the expression changes of miRNAs. Results: Twenty-one differentially expressed miRNAs were identified. Nine differentially expressed miRNAs (hsa-miR-506, hsa-miR-1285, hsa-miR-512-3P, hsa-miR-138, hsa-miR-485-5P, hsa-miR-4262, hsa-miR-548c-3P, has-miR-548a-5P and kshv-miR-K12-1), involved in multiple functions and pathways, were selected for real-time RT-PCR confirmation. Moreover, two significantly important subpathways (neurotrophin signaling pathway and inositol phosphate metabolism) were predicted. Conclusion: The screened differentially expressed miRNAs may be involved in the development of ACM. Specific miRNAs, such as miR-138, may be considered as a new target for the early diagnosis and treatment of human ACM.

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Insight into Liver lncRNA and mRNA Profiling at Four Developmental Stages in Ningxiang Pig

Biology ◽

10.3390/biology10040310 ◽

2021 ◽

Vol 10 (4) ◽

pp. 310

Author(s):

Yan Gong ◽

Yuebo Zhang ◽

Biao Li ◽

Yu Xiao ◽

Qinghua Zeng ◽

...

Keyword(s):

Target Genes ◽

Developmental Stages ◽

Expression Profiles ◽

Regulatory Element ◽

Critical Role ◽

Hunan Province ◽

Messenger Rnas ◽

Regulatory Relationship ◽

Lncrna Expression ◽

Short Time

Ningxiang pigs, a fat-type pig, are native to Ningxiang County in Hunan Province, with thousands of years of breeding history. This study aims to explore the expression profiles and functional networks on messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) in the liver. Liver tissue of Ningxiang piglets was collected at 30, 90, 150, and 210 days after birth (four development stages), and the mRNA and lncRNA expression was profiled. Compared to mRNA and lncRNA expression profiles, most differentially expressed mRNAs (DEmRNAs) were upregulated at 30 days; however, most DElncRNAs were downregulated at 210 days. Via Short Time-series Expression Miner (STEM) analysis and weighted gene co-expression network analysis (WGCNA), a complex interaction between mRNAs and lncRNAs was identified, indicating that lncRNAs may be a critical regulatory element for mRNAs. One module of genes in particular (module profile 4) was related to fibril organization, vasculogenesis, GTPase activator activity, and regulation of kinase activity. The mRNAs and lncRNAs in module profile 4 had a similar pattern of expression, indicating that they have functional and regulatory relationships. Only CAV1, PACSIN2, and CDC42 in the particular mRNA profile 4 were the target genes of lncRNAs in that profile, which shows the possible regulatory relationship between lncRNAs and mRNAs. The expression of these genes and lncRNAs in profile 4 was the highest at 30 days, and it is believed that these RNAs may play a critical role during the suckling period in order to meet the dietary requirements of piglets. In the lncRNA–mRNA co-expression network, the identified gene hubs and associated lncRNAs were shown to be involved in saccharide, lipid, and glucose metabolism, which may play an important role in the development and health of the liver. This result will lead to further investigation of liver lncRNA functions at various stages of development in Ningxiang pigs.

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Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation

PeerJ ◽

10.7717/peerj.7025 ◽

2019 ◽

Vol 7 ◽

pp. e7025 ◽

Cited By ~ 4

Author(s):

Wei Cao ◽

Dan Zhou ◽

Weiwei Tang ◽

Hanxiang An ◽

Yun Zhang

Keyword(s):

Gastric Cancer ◽

Messenger Rna ◽

Target Genes ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Clinical Validation ◽

Diagnostic Efficiency ◽

Messenger Rnas ◽

Diagnostic Efficacy ◽

Expression Levels

BackgroundGastric cancer (GC) is the third leading cause of cancer-related death worldwide, partially due to the lack of effective screening strategies. Thus, there is a stringent need for non-invasive biomarkers to improve patient diagnostic efficiency in GC.MethodsThis study initially filtered messenger RNAs (mRNAs) as prospective biomarkers through bioinformatics analysis. Clinical validation was conducted using circulating mRNA in plasma from patients with GC. Relationships between expression levels of target genes and clinicopathological characteristics were calculated. Then, associations of these selected biomarkers with overall survival (OS) were analyzed using the Kaplan-Meier plotter online tool.ResultsBased on a comprehensive analysis of transcriptional expression profiles across 5 microarrays, top 3 over- and underexpressed mRNAs in GC were generated. Compared with normal controls, expression levels ofcollagen type VI alpha 3 chain(COL6A3),serpin family H member 1 (SERPINH1)andpleckstrin homology and RhoGEF domain containing G1 (PLEKHG1)were significantly upregulated in GC plasmas. Receiver-operating characteristic (ROC) curves on the diagnostic efficacy of plasmaCOL6A3,SERPINH1andPLEKHG1mRNAs in GC showed that the area under the ROC (AUC) was 0.720, 0.698 and 0.833, respectively. Combined, these three biomarkers showed an elevated AUC of 0.907. Interestingly, the higherCOL6A3level was significantly correlated with lymph node metastasis and poor prognosis in GC patients. High level ofSERPINH1mRNA expression was correlated with advanced age, poor differentiation, lower OS, andPLEKHG1was also associated with poor OS in GC patients.ConclusionOur results suggested that circulatingCOL6A3,SERPINH1andPLEKHG1mRNAs could be putative noninvasive biomarkers for GC diagnosis and prognosis.

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