Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5
BACKGROUND: N6-methyladenosine (m6A) RNA regulators play important roles in cancers, but their functions and mechanism have not been demonstrated clearly in gastric cancer (GC). METHODS: In this study, the GC samples with clinical information and RNA transcriptome were downloaded from The Cancer Gen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853004/ https://www.ncbi.nlm.nih.gov/pubmed/36686788 http://dx.doi.org/10.3389/fonc.2022.1079402 |
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author | Ji, Tiannan Gao, Xiaohui Li, Dan Huai, Siyuan Chi, Yajing An, Xian Ji, Wenyu Yang, Siming Li, Jianxiong |
author_facet | Ji, Tiannan Gao, Xiaohui Li, Dan Huai, Siyuan Chi, Yajing An, Xian Ji, Wenyu Yang, Siming Li, Jianxiong |
author_sort | Ji, Tiannan |
collection | PubMed |
description | BACKGROUND: N6-methyladenosine (m6A) RNA regulators play important roles in cancers, but their functions and mechanism have not been demonstrated clearly in gastric cancer (GC). METHODS: In this study, the GC samples with clinical information and RNA transcriptome were downloaded from The Cancer Genome Atlas database. The different expression genes were compared by the absolute value and median ± standard deviation. Samples with complete information were randomly divided into a training dataset and a test dataset. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in the training dataset and constructed a risk model by Cox and least absolute shrinkage and selection operator regression. The model was testified in test datasets, overall survival (OS) was compared with the Kaplan–Meier method, and immune cell infiltration was calculated by the CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. The protein levels of ALKBH5 were detected with immunohistochemistry. The relative expression of messenger-ribonucleic acid (mRNA) was detected with quantitative polymerase chain reaction. RESULTS: ALKBH5 was the only regulator whose expression was lower in tumor samples than that in normal samples. The low expression of ALKBH5 led to the poor OS of GC patients and seemed to be an independent protective factor. The model based on ALKBH5-regulated genes was validated in both datasets (training/test) and displayed a potential capacity to predict a clinical prognosis. Gene Ontology analysis implied that the DEGs were involved in the immune response; CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. The protein levels of ALKBH5 were verified as lowly expressed in GC tissues. SLC7A2 and CGB3 were downregulated with ALKBH5 knockdown. CONCLUSIONS: In this study, we found that ALKBH5 might be a suppressor of GC; ALKBH5 and its related genes were latent biomarkers and immunotherapy targets. |
format | Online Article Text |
id | pubmed-9853004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98530042023-01-21 Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 Ji, Tiannan Gao, Xiaohui Li, Dan Huai, Siyuan Chi, Yajing An, Xian Ji, Wenyu Yang, Siming Li, Jianxiong Front Oncol Oncology BACKGROUND: N6-methyladenosine (m6A) RNA regulators play important roles in cancers, but their functions and mechanism have not been demonstrated clearly in gastric cancer (GC). METHODS: In this study, the GC samples with clinical information and RNA transcriptome were downloaded from The Cancer Genome Atlas database. The different expression genes were compared by the absolute value and median ± standard deviation. Samples with complete information were randomly divided into a training dataset and a test dataset. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in the training dataset and constructed a risk model by Cox and least absolute shrinkage and selection operator regression. The model was testified in test datasets, overall survival (OS) was compared with the Kaplan–Meier method, and immune cell infiltration was calculated by the CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. The protein levels of ALKBH5 were detected with immunohistochemistry. The relative expression of messenger-ribonucleic acid (mRNA) was detected with quantitative polymerase chain reaction. RESULTS: ALKBH5 was the only regulator whose expression was lower in tumor samples than that in normal samples. The low expression of ALKBH5 led to the poor OS of GC patients and seemed to be an independent protective factor. The model based on ALKBH5-regulated genes was validated in both datasets (training/test) and displayed a potential capacity to predict a clinical prognosis. Gene Ontology analysis implied that the DEGs were involved in the immune response; CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. The protein levels of ALKBH5 were verified as lowly expressed in GC tissues. SLC7A2 and CGB3 were downregulated with ALKBH5 knockdown. CONCLUSIONS: In this study, we found that ALKBH5 might be a suppressor of GC; ALKBH5 and its related genes were latent biomarkers and immunotherapy targets. Frontiers Media S.A. 2023-01-06 /pmc/articles/PMC9853004/ /pubmed/36686788 http://dx.doi.org/10.3389/fonc.2022.1079402 Text en Copyright © 2023 Ji, Gao, Li, Huai, Chi, An, Ji, Yang and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ji, Tiannan Gao, Xiaohui Li, Dan Huai, Siyuan Chi, Yajing An, Xian Ji, Wenyu Yang, Siming Li, Jianxiong Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title | Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title_full | Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title_fullStr | Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title_full_unstemmed | Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title_short | Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5 |
title_sort | identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6a demethylase alkbh5 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853004/ https://www.ncbi.nlm.nih.gov/pubmed/36686788 http://dx.doi.org/10.3389/fonc.2022.1079402 |
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