High expression of COMMD7 is an adverse prognostic factor in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a frequent malignancy in adults worldwide; identifying preferable biomarkers has become one of the current challenges. Given that COMMD7 has been reported associated with tumor progression in various human solid cancers but rarely reported in AML, herein, RNA sequencing data from TCGA and GTEx were obtained for analysis of COMMD7 expression and differentially expressed gene (DEG). Furthermore, functional enrichment analysis of COMMD7-related DEGs was performed by GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of COMMD7 in AML was figured out by Kaplan-Meier Cox regression and prognostic nomogram model. R package was used to analyze incorporated studies. As a result, COMMD7 was highly expressed in various malignancies, including AML, compared with normal samples. Moreover, high expression of COMMD7 was associated with poor prognosis in 151 AML samples, as well as subgroups with age >60, NPM1 mutation-positive, FLT3 mutation-negative, and DNMT3A mutation-negative, et al. (P < 0.05). High COMMD7 was an independent prognostic factor in Cox regression analysis; Age and cytogenetics risk were included in the nomogram prognostic model. Furthermore, a total of 529 DEGs were identified between the high- and the low- expression group, of which 92 genes were up-regulated and 437 genes were down-regulated. Collectively, high expression of COMMD7 is a potential biomarker for adverse outcomes in AML. The DEGs and pathways recognized in the study provide a preliminary grasp of the underlying molecular mechanisms of AML carcinogenesis and progression.

Keywords: COMMD7; R packages; The Cancer Genome Atlas; acute myeloid leukemia.

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Figures

Figure 1

The higher expression of COMMD7 was showed in AML compared with normal samples. (A) Expression level of COMMD7 in paired normal and pan-cancer samples. (B) Expression level of COMMD7 in paired normal and AML samples. Analysis between two groups: Wilcoxon Rank sum test; NS: P 0.05 or higher; *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 2

A total of 529 DEGs were identified as being statistically significant between COMMD7 high-expressed and low-expressed groups. (A) Volcano plot of differentially expressed genes, including 92 up-regulated and 437 down-regulated genes. Normalized expression levels were shown in descending order from green to red. (B) Heat map of the 10 differentially expressed RNAs, including 5 up-regulated genes and 5 down-regulated genes. The X-axis represents the samples, while the Y-axis denotes the differentially expressed RNAs. Green and red tones represented down-regulated and up-regulated genes, respectively.

Figure 3

GO/KEGG enrichment analysis of DEGs between high- and low- COMMD7 expression in TCGA-LAML patients. (A) Enriched GO terms in the “biological process” category; (B) Enriched GO terms in the “molecular function” category. (C) Enriched GO terms in the “cellular component” category; (D) KEGG pathway annotations. The X-axis represented the proportion of DEGs, and the Y-axis represented different categories. The different colors indicate different properties, and the different sizes represent the number of DEGs.

Figure 4

Enrichment plots from the gene set enrichment analysis (GSEA). (A–L) ES, enrichment score; NES, normalized ES; ADJ P-val, adjusted P-value.

Figure 5

The expression of COMMD7 was associated with immune infiltration in the AML microenvironment. (A), The forest plots showed a positive correlation between COMMD7 and 13 immune cells, and a negative correlation between COMMD7 and 11 immune cell subsets. The size of dots showed the absolute value of Spearman r. (B) Correlation between the relative enrichment score of NK CD56(bright) cells and the expression level (TPM) of COMMD7. (C) Infiltration of NK CD56(bright) cells between low- and high-COMMD7 expressed.

Figure 6

The PPI network of COMMD7-related DEGs and the most significant module. (A) The PPI network of DEGs was constructed using Cytoscape. (B) The most significant module was obtained from PPI network with 42 nodes and 150 edges.

Figure 7

Association between COMMD7 expression and clinical features and cytogenetic risks. (A) The diagnostic efficacy of COMMD7 in acute myelogenous leukemia analyzed by ROC. (B–H) Association between COMMD7 expression and BM blasts (20%), WBC counts (20 × 109), FAB classification, cytogenetics risk, NPM1 mutation, FLT3 mutation, and IDH1 R132 mutation analyzed by using Wilcoxon Rank SUM test.

Figure 8

High expression of COMMD7 was associated with poor OS in AML patients. (A) Kaplan-Meier curves in all AML patients. (B) Kaplan-Meier curves in AML patients with BM blasts > 20%. (C) Kaplan-Meier curves in AML patients with PB blasts ≤ 70%. (D) Kaplan-Meier curves in AML patients with age ≥ 60. (E–L) Kaplan-Meier curves in subgroups with FLT3 mutation-negative, IDH1 R132 mutation-positive, IDH1 R140 mutation-positive, R172 mutation-positive, NPM1 mutation-positive, RAS mutation-positive, RUX1 mutation-negative, and DNMT3A mutation-negative in AML patients.

Figure 9

Forest plot showed that COMMD7 predicted poor prognosis in the subgroup of WBC count (>20 × 109/L) (HR = 2.062, P = 0.030), BM blasts (>20%) (HR = 1.897, P = 0.024), PB blasts (>70%) (HR = 2.435, P = 0.007), FLT3 mutation negative (HR = 3.330, p = 0.009), and NPM1 mutation positive (HR = 2.345, P < 0.001).

Figure 10

A prognostic predictive model of COMMD7 in AML. (A) Nomogram for predicting the probability of 1-, 3-, 5-year OS for AML. (B) Calibration plot of the nomogram for predicting the probability of OS at 1, 3, and 5 years.