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Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis

BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE:...

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Autores principales: Yan, Jianing, Ye, Guoliang, Jin, Yanping, Miao, Min, Li, Qier, Zhou, Hanxuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262520/
https://www.ncbi.nlm.nih.gov/pubmed/37312060
http://dx.doi.org/10.1186/s12864-023-09421-2
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author Yan, Jianing
Ye, Guoliang
Jin, Yanping
Miao, Min
Li, Qier
Zhou, Hanxuan
author_facet Yan, Jianing
Ye, Guoliang
Jin, Yanping
Miao, Min
Li, Qier
Zhou, Hanxuan
author_sort Yan, Jianing
collection PubMed
description BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. METHODS: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. RESULTS: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. CONCLUSIONS: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09421-2.
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spelling pubmed-102625202023-06-15 Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis Yan, Jianing Ye, Guoliang Jin, Yanping Miao, Min Li, Qier Zhou, Hanxuan BMC Genomics Research BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. METHODS: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. RESULTS: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. CONCLUSIONS: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09421-2. BioMed Central 2023-06-13 /pmc/articles/PMC10262520/ /pubmed/37312060 http://dx.doi.org/10.1186/s12864-023-09421-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yan, Jianing
Ye, Guoliang
Jin, Yanping
Miao, Min
Li, Qier
Zhou, Hanxuan
Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title_full Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title_fullStr Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title_full_unstemmed Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title_short Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
title_sort identification of novel prognostic circrna biomarkers in circrna-mirna-mrna regulatory network in gastric cancer and immune infiltration analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262520/
https://www.ncbi.nlm.nih.gov/pubmed/37312060
http://dx.doi.org/10.1186/s12864-023-09421-2
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