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Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis
BACKGROUND: Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown. AIM: To elucidate the molecular characteristics of IGC at the proteomics level. METHODS: Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Baishideng Publishing Group Inc
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694269/ https://www.ncbi.nlm.nih.gov/pubmed/36438703 http://dx.doi.org/10.4251/wjgo.v14.i11.2097 |
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author | Zhang, Li-Hua Zhuo, Hui-Qin Hou, Jing-Jing Zhou, Yang Cheng, Jia Cai, Jian-Chun |
author_facet | Zhang, Li-Hua Zhuo, Hui-Qin Hou, Jing-Jing Zhou, Yang Cheng, Jia Cai, Jian-Chun |
author_sort | Zhang, Li-Hua |
collection | PubMed |
description | BACKGROUND: Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown. AIM: To elucidate the molecular characteristics of IGC at the proteomics level. METHODS: Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry. The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software. The differentially expressed proteins (DEPs) were screened using |log2(Fold change)| > 1 and P-adj < 0.01 as the thresholds. The expression levels of selected proteins were verified by Western blotting. The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software. The DEPs were functionally annotated using clusterProfiler, STRING and DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. P < 0.05 was considered statistically significant. RESULTS: A total of 7361 DEPs were identified, of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues. The top 10 up-regulated proteins were MRTO4, BOP1, PES1, WDR12, BRIX1, NOP2, POLR1C, NOC2L, MYBBP1A and TSR1, and the top 10 down-regulated proteins were NDUFS8, NDUFS6, NDUFA8, NDUFA5, NDUFC2, NDUFB8, NDUFB5, NDUFB9, UQCRC2 and UQCRC1. The up-regulated proteins were enriched for 9 biological processes including DNA replication, ribosome biogenesis and initiation of DNA replication, and the cellular component MCM complex. Among the down-regulated proteins, 17 biological processes were enriched, including glucose metabolism, pyruvic acid metabolism and fatty acid β-oxidation. In addition, the mitochondrial inner membrane, mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components, and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity, acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched. The significant KEGG pathways for the up-regulated proteins were DNA replication, cell cycle and mismatch repair, whereas 18 pathways including oxidative phosphorylation, fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins. CONCLUSION: The proteins involved in cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC, and the proteomic profile may enable the discovery of novel biomarkers. |
format | Online Article Text |
id | pubmed-9694269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-96942692022-11-26 Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis Zhang, Li-Hua Zhuo, Hui-Qin Hou, Jing-Jing Zhou, Yang Cheng, Jia Cai, Jian-Chun World J Gastrointest Oncol Basic Study BACKGROUND: Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown. AIM: To elucidate the molecular characteristics of IGC at the proteomics level. METHODS: Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry. The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software. The differentially expressed proteins (DEPs) were screened using |log2(Fold change)| > 1 and P-adj < 0.01 as the thresholds. The expression levels of selected proteins were verified by Western blotting. The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software. The DEPs were functionally annotated using clusterProfiler, STRING and DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. P < 0.05 was considered statistically significant. RESULTS: A total of 7361 DEPs were identified, of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues. The top 10 up-regulated proteins were MRTO4, BOP1, PES1, WDR12, BRIX1, NOP2, POLR1C, NOC2L, MYBBP1A and TSR1, and the top 10 down-regulated proteins were NDUFS8, NDUFS6, NDUFA8, NDUFA5, NDUFC2, NDUFB8, NDUFB5, NDUFB9, UQCRC2 and UQCRC1. The up-regulated proteins were enriched for 9 biological processes including DNA replication, ribosome biogenesis and initiation of DNA replication, and the cellular component MCM complex. Among the down-regulated proteins, 17 biological processes were enriched, including glucose metabolism, pyruvic acid metabolism and fatty acid β-oxidation. In addition, the mitochondrial inner membrane, mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components, and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity, acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched. The significant KEGG pathways for the up-regulated proteins were DNA replication, cell cycle and mismatch repair, whereas 18 pathways including oxidative phosphorylation, fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins. CONCLUSION: The proteins involved in cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC, and the proteomic profile may enable the discovery of novel biomarkers. Baishideng Publishing Group Inc 2022-11-15 2022-11-15 /pmc/articles/PMC9694269/ /pubmed/36438703 http://dx.doi.org/10.4251/wjgo.v14.i11.2097 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Zhang, Li-Hua Zhuo, Hui-Qin Hou, Jing-Jing Zhou, Yang Cheng, Jia Cai, Jian-Chun Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title | Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title_full | Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title_fullStr | Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title_full_unstemmed | Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title_short | Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
title_sort | proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694269/ https://www.ncbi.nlm.nih.gov/pubmed/36438703 http://dx.doi.org/10.4251/wjgo.v14.i11.2097 |
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