The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma
Abstract Background RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation...
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Language: | English |
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BMC
2023-05-01
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Series: | BMC Gastroenterology |
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Online Access: | https://doi.org/10.1186/s12876-023-02776-6 |
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author | Ting Liu Lei Sun Zhi-zhao Li Kun Yang Jia-min Chen Xiao-yi Han Li-ming Qi Xin-gang Zhou Peng Wang |
author_facet | Ting Liu Lei Sun Zhi-zhao Li Kun Yang Jia-min Chen Xiao-yi Han Li-ming Qi Xin-gang Zhou Peng Wang |
author_sort | Ting Liu |
collection | DOAJ |
description | Abstract Background RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. Method The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan–Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis(DCA)analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. Result The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. Conclusion We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies. |
first_indexed | 2024-04-09T12:49:30Z |
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institution | Directory Open Access Journal |
issn | 1471-230X |
language | English |
last_indexed | 2024-04-09T12:49:30Z |
publishDate | 2023-05-01 |
publisher | BMC |
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series | BMC Gastroenterology |
spelling | doaj.art-772cfc2439484fb6b832c0d35a77f6532023-05-14T11:18:48ZengBMCBMC Gastroenterology1471-230X2023-05-0123111210.1186/s12876-023-02776-6The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinomaTing Liu0Lei Sun1Zhi-zhao Li2Kun Yang3Jia-min Chen4Xiao-yi Han5Li-ming Qi6Xin-gang Zhou7Peng Wang8Department of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Cardiovascular, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Ditan Hospital, Capital Medical UniversityAbstract Background RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. Method The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan–Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis(DCA)analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. Result The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. Conclusion We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.https://doi.org/10.1186/s12876-023-02776-6m6A/ m5C/m1A regulatory genesHepatocellular carcinomaPrognostic modelTumor immune microenvironment |
spellingShingle | Ting Liu Lei Sun Zhi-zhao Li Kun Yang Jia-min Chen Xiao-yi Han Li-ming Qi Xin-gang Zhou Peng Wang The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma BMC Gastroenterology m6A/ m5C/m1A regulatory genes Hepatocellular carcinoma Prognostic model Tumor immune microenvironment |
title | The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
title_full | The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
title_fullStr | The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
title_full_unstemmed | The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
title_short | The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
title_sort | m6a m5c m1a regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma |
topic | m6A/ m5C/m1A regulatory genes Hepatocellular carcinoma Prognostic model Tumor immune microenvironment |
url | https://doi.org/10.1186/s12876-023-02776-6 |
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