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. 2022 Feb 11:13:822261.
doi: 10.3389/fgene.2022.822261. eCollection 2022.

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

Kaijie Chen  1   2 , Dongjie Shen  3 , Lin Tan  4 , Donglin Lai  1   2 , Yuru Han  1   2 , Yonggang Gu  5 , Changlian Lu  1 , Xuefeng Gu  1   2   6
Affiliations

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

Kaijie Chen et al. Front Genet. .

Abstract

Recent studies have identified a role for ALKBH7 in the occurrence and progression of cancer, and this protein is related to cellular immunity and immune cell infiltration. However, the prognostic and immunotherapeutic value of ALKBH7 in different cancers have not been explored. In this study, we observed high ALKBH7 expression in 17 cancers and low expression in 5 cancers compared to paired normal tissues. Although ALKBH7 expression did not correlate relatively significantly with the clinical parameters of age (6/33), sex (3/33) and stage (3/27) in the cancers studied, the results of the survival analysis reflect the pan-cancer prognostic value of ALKBH7. In addition, ALKBH7 expression was significantly correlated with the TMB (7/33), MSI (13/33), mDNAsi (12/33) and mRNAsi (13/33) in human cancers. Moreover, ALKBH7 expression was associated and predominantly negatively correlated with the expression of immune checkpoint (ICP) genes in many cancers. Furthermore, ALKBH7 correlated with infiltrating immune cells and ESTIMATE scores, especially in PAAD, PRAD and THCA. Finally, the ALKBH7 gene coexpression network is involved in the regulation of cellular immune, oxidative, phosphorylation, and metabolic pathways. In conclusion, ALKBH7 may serve as a potential prognostic pan-cancer biomarker and is involved in the immune response. Our pan-cancer analysis provides insight into the role of ALKBH7 in different cancers.

Keywords: ALKBH7; immune infiltration; immunotherapy; pan-cancer; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The analysis and indicators employed in our research. In clinical correlation section, differential ALKBH7 expression analyses were performed between different tissues (tumor versus normal), ages (≤60 versus >60), genders (male versus female), stages (stage I + II versus stage III + IV). Prognostic analysis was based on univariate Cox regression and Kaplan-Meier survival curve. In immune mechanism section, relevant signaling pathways were explored by GSEA based on the ALKBH7 expression.
FIGURE 2
FIGURE 2
The clinical correlation of ALKBH7 expression. (A) Differential expression of ALKBH7 in normal and tumor samples from patients with 33 cancers; the correlations of ALKBH7 with age (B), sex (C) and stage (D) in 33 cancers. “*” indicates p < 0.05, “**” indicates p < 0.01 and “***” indicates p < 0.001.
FIGURE 3
FIGURE 3
Representative ALKBH7 immunohistochemical staining in tumor and normal tissues. The expression of ALKBH7 gene in BRCA (A), LUAD (B), LUSC (C), OV (D), PRAD (E), and UCEC (F) is significantly higher than that in the corresponding normal tissues.
FIGURE 4
FIGURE 4
Associations between ALKBH7 expression and OS of patients with cancer. (A) Forest plot showing the hazard ratios of ALKBH7 in 33 cancers; Kaplan-Meier survival curves of OS forpatients stratified according to different ALKBH7 expression profiles in KIRP (B), LAML (C), MESO (D), SARC (E) and UCEC (F).
FIGURE 5
FIGURE 5
Associations between ALKBH7 expression and DSS of patients with cancer. (A) Forest plot showing hazard ratios of ALKBH7 in 32 cancers; Kaplan-Meier survival curves of DSS forpatients stratified according to different ALKBH7 expression profiles in BLCA (B), KIRC (C), KIRP (D), MESO (E) and UCEC (F).
FIGURE 6
FIGURE 6
The relationship between ALKBH7 expression and immune subtypes in BLCA (A), BRCA (B), KIRC (C), LIHC (D), PRAD (E), SKCM (F), TGCT (G) and UCEC (H). [C1 (wound healing); C2 (IFN-gamma dominant); C3 (inflammatory); C4 (lymphocyte depleted); C5 (immunologically quiet); C6 (TGF-beta dominant)].
FIGURE 7
FIGURE 7
The relationship between ALKBH7 expression and molecular subtypes in BRCA (A), COAD (B), HNSC (C), KIRP (D), LGG (E), LUSC (F), OV (G), PRAD (H), STAD (I) and UCEC (J).
FIGURE 8
FIGURE 8
Correlations between the expression of ALKBH7 and immune checkpoint genes in 33 types of cancer. “*” indicates p < 0.05, “**” indicates p < 0.01 and “***” indicates p < 0.001.
FIGURE 9
FIGURE 9
The correlation between ALKBH7 expression and the TMB (A), MSI (B), mDNAsi (C), and mRNAsi (D). “*” indicates p < 0.05, “**” indicates p < 0.01 and “***” indicates p < 0.001.
FIGURE 10
FIGURE 10
Correlations between ALKBH7 expression and both immune cell infiltration and ESTIMATE score. (A) The relationship between the ALKBH7 expression level and numbers of infiltrating B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, dendritic cell in human cancers. (B) The relationship between ALKBH7 expression and the ESTIMATE score in human cancers. (C) Correlation of ALKBH7 expression with immune cell infiltration levels in PAAD, PRAD, and THCA. (D) Correlation of ALKBH7 expression with ESTIMATE scores in PAAD, PRAD, and THCA.
FIGURE 11
FIGURE 11
Heat map of the correlations between ALKBH7 expression and immune cell subtypes in 33 types of cancer. “*” indicates p < 0.05, “**” indicates p < 0.01 and “***” indicates p < 0.001.
FIGURE 12
FIGURE 12
KEGG enrichment analysis of ALKBH7. (A) Top 20 enriched KEGG pathways in PAAD. (B) Top 20 enriched KEGG pathways in PRAD. (C) Top 20 enriched KEGG pathways in THCA.
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