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Meta-Analysis
. 2020 Dec;9(23):8782-8800.
doi: 10.1002/cam4.3486. Epub 2020 Sep 26.

Diagnostic significance and carcinogenic mechanism of pan-cancer gene POU5F1 in liver hepatocellular carcinoma

Dingdong He  1 , Xiaokang Zhang  1 , Jiancheng Tu  1
Affiliations
Meta-Analysis

Diagnostic significance and carcinogenic mechanism of pan-cancer gene POU5F1 in liver hepatocellular carcinoma

Dingdong He et al. Cancer Med. 2020 Dec.

Abstract

Background: The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and functional mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly.

Methods: An integrative strategy of meta-analysis, bioinformatics, and wet-lab approach was used to explore the diagnostic and prognostic significance of POU5F1 in various types of tumors, especially in LIHC. Meta-analysis was utilized to investigate the impact of POU5F1 on prognosis and clinicopathological parameters in various cancers. The expression level and diagnostic value of POU5F1 were assessed by qPCR in plasma collected from LIHC patients and controls. The correlation between POU5F1 and tumor infiltrating immune cells (TIICs) in LIHC was evaluated by CIBERSORT. Gene set enrichment analysis (GSEA) was performed based on TCGA. Hub genes and related pathways were identified on the basis of co-expression genes of POU5F1.

Results: Elevated POU5F1 was associated with poor OS, DFS, RFS, and DSS in various cancers. POU5F1 was confirmed as an independent risk factor for LIHC and correlated with tumor occurrence, stage, and invasion depth. The combination of POU5F1 and AFP in plasma was with high diagnostic validity (AUC = 0.902, p < .001). Specifically, the level of POU5F1 was correlated with infiltrating levels of B cells, T cells, dendritic cells, and monocytes in LIHC. GSEA indicated that POU5F1 participated in multiple cancer-related pathways and cell proliferation pathways. Moreover, CBX3, CCHCR1, and NFYC were filtered as the central hub genes of POU5F1.

Conclusion: Our study identified POU5F1 as a pan-cancer gene that could not only be a prognostic and diagnostic biomarker in various cancers, especially in LIHC, but functionally carcinogenic in LIHC.

Keywords: LIHC; POU5F1; biomarker; immune infiltrates; pathogenesis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Forest plots of HRs for OS, DFS, RFS, and DSS with elevated POU5F1 expression. (A) HRs for OS. (B) HRs for OS subgroup analysis of cancer type. (C) HRs for DFS, RFS, and DSS. (D) HRs for DFS subgroup analysis of cancer type
FIGURE 2
FIGURE 2
Expression status of POU5F1 in various cancers and survival analysis in LIHC. (A) Expression status of POU5F1 in various cancers based on TCGA. Statistical significance was assigned at p < .05 (*), p < .01 (**), p < .001 (***). (B) OS and DFS of LIHC patients with high (n = 182) or low (n = 182) POU5F1 levels in LIHC tissues
FIGURE 3
FIGURE 3
Association between POU5F1 expression and clinicopathologic characteristics and the diagnostic value of POU5F1 in LIHC. (A) Cancer status. (B) Age. (C) Gender. (D) Grade. (E) Clinical stage. (F) Tumor invasion depth. (G) Lymph node metastasis. (H) Distant metastasis. (I) Expression level of POU5F1 in plasma collected from 30 controls and 30 LIHC patients. (J) ROC based on POU5F1 and AFP levels in plasma separately or combinedly
FIGURE 4
FIGURE 4
The proportion of 22 subpopulations of TIICs in normal liver tissues and LIHC tissues. (A) TIICs in normal liver tissues. (B) TIICs in LIHC tissues. Correlation between POU5F1 level and (C) B cells memory, (D) T cells follicular helper, (E) dendritic cells activated, (F) B cells naive, and (G) monocytes
FIGURE 5
FIGURE 5
GSEA for POU5F1 and enrichment analysis of the co‐expression genes of POU5F1 in LIHC. (A) GSEA of POU5F1 based on GO gene sets. (B) GSEA of POU5F1 based on KEGG gene sets. (C) Representative expression heat map of the top 50 co‐expression genes of POU5F1. (D) GO enrichment analysis of the co‐expression genes of POU5F1. (E) KEGG enrichment analysis of the co‐expression genes of POU5F1
FIGURE 6
FIGURE 6
PPI network and the correlation between POU5F1 and the hub genes. (A) PPI network and the nine hub genes interacted with POU5F1. (B) Correlation between expression of POU5F1 and the nine hub gene
FIGURE 7
FIGURE 7
Kaplan–Meier survival analysis of nine hub genes of POU5F1 in LIHC based on TCGA. (A‐I) Overall survival of nine hub genes. (J‐R) Disease‐free survival of nine hub genes
FIGURE 8
FIGURE 8
Expression levels and potential cell signal transduction pathways of POU5F1 and hub genes in LIHC. (A) Expression levels of POU5F1 and the nine hub genes in LIHC. (B) Potential cell signal transduction pathways of POU5F1 and the nine hub genes in LIHC
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