The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.


Journal

BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547

Informations de publication

Date de publication:
11 May 2023
Historique:
received: 21 06 2022
accepted: 20 04 2023
medline: 15 5 2023
pubmed: 12 5 2023
entrez: 11 5 2023
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 METHODS
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 RESULTS
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 CONCLUSIONS
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.

Identifiants

pubmed: 37170222
doi: 10.1186/s12876-023-02776-6
pii: 10.1186/s12876-023-02776-6
pmc: PMC10173529
doi:

Substances chimiques

RNA 63231-63-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

147

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ting Liu (T)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Lei Sun (L)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Zhi-Zhao Li (ZZ)

Department of Cardiovascular, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Kun Yang (K)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Jia-Min Chen (JM)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Xiao-Yi Han (XY)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Li-Ming Qi (LM)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Xin-Gang Zhou (XG)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China. zhouxg1980@126.com.

Peng Wang (P)

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China. chinaroc001@126.com.

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