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

Abstract

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 Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. 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 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.

A prognostic exosome-related LncRNA risk model correlates with the immune microenvironment in liver cancer

“…These results suggested that the five-lncRNA signature might have an important impact on immune cell infiltration. Due to the high degree of malignancy and postoperative recurrence rate of liver cancer, the five-year survival rate is still low (Peng et al, 2021;Yan et al, 2021). In recent years, the emergence of sorafenib and PD-1 inhibitors has greatly prolonged the survival of HCC patients.…”

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

“…ALKBH5 is an RNA demethylation modification enzyme during m6A modification processes ( Cai et al, 2021 ; Peng et al, 2021 ; Wu, et al, 2021 ) and mainly reverses m6A methylation ( Wang et al, 2020b ; Cai et al, 2021 ). ALKBH5 is an Fe 2+ and Q-ketoglutarate-dependent non-heme oxygenase, belongs to the ALKB family, and only displays demethylation activity for m6A modifications on single-stranded RNA/DNA.…”

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of ALKBH7

“…In addition, recent studies have identified a role for ALKBH7 in the progression of several cancers and its relationship with immune cell infiltration. ALKBH7 expression is significantly elevated in hepatocellular carcinoma and negatively correlates with CD4 + cells, macrophages and neutrophils (Peng et al, 2021). ALKBH7 is associated with overall survival in individuals with lung adenocarcinoma and negatively correlates with CD8 + T cells and macrophages (Wu et al, 2021).…”