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, 18 (5), 5119-5128

Exosome Complex Genes Mediate RNA Degradation and Predict Survival in Mantle Cell Lymphoma

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Exosome Complex Genes Mediate RNA Degradation and Predict Survival in Mantle Cell Lymphoma

Weilong Zhang et al. Oncol Lett.

Abstract

Exosome complex (EXOSC) genes, which encode a multi-protein intracellular complex, mediate the degradation of various types of RNA molecules. EXOSCs, also known as polymyositis/scleroderma complexes, exist in eukaryotic cells and archaea, and primarily mediate 3' to 5'mRNA degradation. However, how EXOSC genes are implicated in processes of B-cell immune-associated pathways and B-cell tumorigenesis remains unclear. The present bioinformatics study indicated that 6 of 10 EXOSC genes, particularly the EXO.index, were able to predict the survival of patients with mantle cell lymphoma (MCL), by analyzing gene expression profiles of 123 patients with MCL from the Gene Expression Omnibus database. The results suggested that EXOSC gene expression may be a molecular marker for MCL. Compared with the whole transcript profile, patients with MCL with a high EXO.index exhibited poorer survival and decreased RNA levels, which was also verified in a second dataset. The EXOSC genes may be associated with DNA repair and B-cell activation pathways, which may be the cause of poorer survival of patients with MCL.

Keywords: RNA degradation; exosome complex genes; gene expression profile; mantle cell lymphoma.

Figures

Figure 1.
Figure 1.
Survival analysis and forest plot of 10 EXOSC genes of 123 patients with mantle cell lymphoma. (A) Survival analysis of 10 EXOSC genes, classified by hazard ratio. (B) Forest plot of 10 EXOSC genes, classified by hazard ratio. The forest plot includes the lower and upper 95% confidence intervals. EXOSC, exosome complex. EXOSC5, exosome component 5; EXOSC1, exosome component 1; EXOSC4, exosome component 4; EXOSC2, exosome component 2; EXOSC7, exosome component 7; EXOSC3, exosome component 3; EXOSC8, exosome component 8; EXOSC6, exosome component 6; EXOSC9, exosome component 9; EXOSC10, exosome component 10.
Figure 2.
Figure 2.
Kaplan-Meier curves for 4 EXOSC genes regarding overall survival of 123 patients with mantle cell lymphoma. The p-values for the EXOSC5, EXOSC1, EXOSC4 and EXOSC2 curves were as follows: P=7.0×10−7; P=5.7×10−6; P=1.1×10−4; and P=2.7×10−3, respectively. The log-rank test was used to compare Kaplan-Meier curves. EXOSC, exosome complex; EXOSC5, exosome component 5; EXOSC1, exosome component 1; EXOSC4, exosome component 4; EXOSC2, exosome component 2.
Figure 3.
Figure 3.
Correlation plot of the expression levels of 10 EXOSC genes in mantle cell lymphoma. (A) Correlation plot of 10 EXOSC genes. The Pearson correlation coefficient is presented. The X-axis and Y-axis represent gene expression levels (log2). The colors included in the upper right section of the plot represent dot density. Grey and blue represent mean low dot density and red and yellow represent high dot density. (B) Correlations between EXOSC4 and EXOSC5 (upper left), EXOSC1 and EXOSC5 (upper right), EXOSC7 and EXOSC9 (lower left), EXOSC7 and EXOSC8 (lower right) genes were calculated. EXOSC, exosome complex; cor, Pearson correlation coefficient; EXOSC4, exosome component 4; EXOSC5, exosome component 5; EXOSC1, exosome component 1; EXOSC7, exosome component 7; EXOSC9, exosome component 9; EXOSC8, exosome component 8.
Figure 4.
Figure 4.
A total of 10 EXOSC genes were used as classifiers for the 123 patients with MCL. (A) Unsupervised clustering of the expression of 10 EXOSC genes for the 123 patients with MCL. The cluster of EXOSC genes demonstrated cosine correlation similarity. (B) Fuzzy clustering of the 123 patients with MCL based on the expression of the 10 EXOSC genes. (C) Kaplan-Meier curves for overall survival of 123 patients with MCL based on the EXO.index (P=1.73×10−7). The log-rank test was used to compare Kaplan-Meier curves. EXOSC, exosome complex; EXO.index, exosome complex index; MCL, mantle cell lymphoma; EXOSC5, exosome component 5; EXOSC1, exosome component 1; EXOSC4, exosome component 4; EXOSC2, exosome component 2; EXOSC7, exosome component 7; EXOSC3, exosome component 3; EXOSC8, exosome component 8; EXOSC6, exosome component 6; EXOSC9, exosome component 9; EXOSC10, exosome component 10.
Figure 5.
Figure 5.
Differentially expressed genes between the EXO.index-high and EXO.index-low groups of 123 patients with MCL. (A) The heatmap demonstrates the differentially expressed genes between the EXO.index-high and EXO.index-low groups. The red color represents high expression, the green color represents low expression and the white color represents intermediate expression. The top 12 downregulated and 12 upregulated genes were included. On the right-hand side of the heatmap, the bar graphs on the left indicate the fold changes (log2) and the right bar graph indicates the P-values (-log10). (B) The total of 303 downregulated genes and 153 upregulated genes were identified between the EXO.index-high and EXO.index-low groups of patients with MCL. (C) Cumulative distribution of RNA expression levels of different genes between the EXO.index-high and EXO.index-low groups in patients with MCL (log2 fold change). The left plot represents the GSE93291 dataset (n=123 samples; P=5.14×10−3) and the right plot represents the GSE36000 dataset (n=38 samples; P=9.20×10−7). EXO.index, exosome complex index; MCL, mantle cell lymphoma.
Figure 6.
Figure 6.
Significantly enriched pathways between patients with MCL in the EXO.index-high and EXO.index-low groups. (A) Bar graph displaying the distinctly enriched cell division-associated pathways (left-hand side) and B-cell immune-associated pathways (right-hand side). (B) Differentially expressed genes in the DNA repair pathway between EXO.index-high and EXO.index-low groups in patients with MCL. The left plot represents the GSE93291 dataset (n=123 samples; P<0.05), and the right plot is for the GSE36000 dataset (n=38 samples; P<0.05). EXO.index, exosome complex index; MCL, mantle cell lymphoma; FANCA, FA complementation group A; INO80D, INO80 complex subunit D.

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