The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma.

AlkB family Hepatocellular carcinoma Immune cell infiltration Molecular profiles Prognosis

Journal

PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425

Informations de publication

Date de publication:
2021
Historique:
received: 09 07 2021
accepted: 16 08 2021
entrez: 24 9 2021
pubmed: 25 9 2021
medline: 25 9 2021
Statut: epublish

Résumé

Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Several bioinformatics tools and In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

Sections du résumé

BACKGROUND BACKGROUND
Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known.
METHODS METHODS
Several bioinformatics tools and
RESULTS RESULTS
In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues.
CONCLUSIONS CONCLUSIONS
Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

Identifiants

pubmed: 34557360
doi: 10.7717/peerj.12123
pii: 12123
pmc: PMC8418211
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e12123

Informations de copyright

©2021 Peng et al.

Déclaration de conflit d'intérêts

The authors declare there are no competing interests.

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Auteurs

Bi Peng (B)

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Yuanliang Yan (Y)

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Zhijie Xu (Z)

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Classifications MeSH