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. 2022 Jan 31:12:819520.
doi: 10.3389/fgene.2021.819520. eCollection 2021.

Prognostic Biomarker DDOST and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma

Changyu Zhu  1 , Hua Xiao  2   3 , Xiaolei Jiang  4 , Rongsheng Tong  2   3 , Jianmei Guan  5
Affiliations

Prognostic Biomarker DDOST and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma

Changyu Zhu et al. Front Genet. .

Abstract

Background: Dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit (DDOST) is an important enzyme in the process of high-mannose oligosaccharide transferring in cells. Increasing DDOST expression is associated with impairing liver function and the increase of hepatic fibrosis degrees, hence exacerbating the liver injury. However, the relation between DDOST and hepatocellular carcinoma (HCC) has not been revealed yet. Method: In this study, we evaluated the prognostic value of DDOST in HCC based on data from The Cancer Genome Atlas (TCGA) database. The relationship between DDOST expression and clinical-pathologic features was evaluated by logistic regression, the Wilcoxon signed-rank test, and Kruskal-Wallis test. Prognosis-related factors of HCC including DDOST were evaluated by univariate and multivariate Cox regression and the Kaplan-Meier method. DDOST-related key pathways were identified by gene set enrichment analysis (GSEA). The correlations between DDOST and cancer immune infiltrates were investigated by the single-sample gene set enrichment analysis (ssGSEA) of TCGA data. Results: High DDOST expression was associated with poorer overall survival and disease-specific survival of HCC patients. GSEA suggested that DDOST is closely correlated with cell cycle and immune response via the PPAR signaling pathway. ssGSEA indicated that DDOST expression was positively correlated with the infiltrating levels of Th2 cells and negatively correlated with the infiltration levels of cytotoxic cells. Conclusion: All those findings indicated that DDOST was correlated with prognosis and immune infiltration in HCC.

Keywords: DDOST; HCC; T helper cells; prognosis; tumor-infiltration.

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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 results of differentially expressed gene (DEG) analysis. (A) The volcano plot of differentially expressed RNAs. (B,C) The different expressions of DDOST between HCC and the normal group. (D) The heat map of the 25 genes correlated to DDOST.
FIGURE 2
FIGURE 2
Enrichment analysis of DDOST in HCC. (A) Biological process enrichment related to DDOST-related genes. (B) A network of DDOST and its 20 potential co-interaction proteins. (C–F) The results of enrichment analysis from GSEA.
FIGURE 3
FIGURE 3
The results of analysis between DDOST expression and immune infiltration. (A) The positive correlation between DDOST expression and Th2 cells. (B) Th2 cells’ infiltration level in different DDOST expression groups. (C) The negative correlation between DDOST expression and cytotoxic cells. (D) Cytotoxic cells’ infiltration level in different DDOST expression groups. (E) Correlation between DDOST expression level and the relative abundances of 24 immune cells. (F) Heat map of 24 immune infiltration cells in HCC.
FIGURE 4
FIGURE 4
Association between the DDOST expression and different clinicopathologic characteristics. (A) Association between the DDOST expression and the pathologic stage of HCC, (B) T stage, (C) OS event, (D) vascular invasion, and (E) histologic grade.
FIGURE 5
FIGURE 5
The prognostic value of DDOST in LIHC. (A) Multivariate Cox regression visualized in the forest plot (B) DDOST expression distribution and survival status. 0: dead, 1: alive. (C) Diagnostic ROC curve of DDOST. (D) Time-dependent ROC curve of DDOST.
FIGURE 6
FIGURE 6
The prognostic value of DDOST in the different subgroups. (A,B) The prognostic value of DDOST in OS and DSS of HCC. (C–G) High expression of DDOST was associated with worse OS in different subgroups.
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