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Medicine (Baltimore)
2020 Dec 04;9949:e23554. doi: 10.1097/MD.0000000000023554.
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Overexpression of TPX2 predicts poor clinical outcome and is associated with immune infiltration in hepatic cell cancer.
Zhu H
,
Liu J
,
Feng J
,
Zhang Q
,
Bian T
,
Li X
,
Sun H
,
Zhang J
,
Liu Y
.
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Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been identified as an oncogene in multiple cancers. However, the associations among TPX2 expression, prognosis, and tumor immunity in hepatic cell cancer (HCC) have not been explored. We analyzed TPX2 expression by multiple gene expression databases, including Oncomine, TIMER, and UALCAN. The prognosis effect of TPX2 was analyzed by Kaplan--Meier plotter. The coexpressed genes with TPX2 were analyzed using Linked Omics. The association among TPX2 and immune infiltrates and immune checkpoints was determined by TIMER. It was found that TPX2 expression was notably upregulated in multiple HCC tissues. Overexpression of TPX2 has associations with race, age, weight, clinical stage and tumor grade, as well as poor prognosis in overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS). In addition, TPX2 expression has a positive association with the infiltration of immune cells and the expression of immune checkpoint molecules. Coexpressed genes and functional network analysis suggested several potential mechanisms of TPX2 affecting HCC progression. The findings reveal that TPX2 has associations with prognosis and infiltration of immune cells in HCC patients, which has laid a basis for in-depth study of TPX2 role in HCC.
Figure 1. Expression of TPX2 in different types of human cancers. (A) Dysregulated expressions of TPX2 in datasets of different cancers compared with normal tissues are examined by Oncomine. (B) The TPX2 expression levels in different tumor types from the TCGA database in TIMER. âPâ<â.05, â Pâ<â.01, â¡Pâ<â.001. âTotal Unique Analysesâ is defined as total analyses included in the Oncomine database. âTotal Unique Analysesâ is defined as analyses that meet our stated threshold values.
Figure 2. TPX2 expression level in HCC. (A) Chart and box plot showing the expression of TPX2 in cancerous tissues and the adjacent normal tissues, according to t test in HCCDB. (B) The protein expression of TPX2 in HCC from HPA. (C) Distribution of TPX2 protein expression level in HCC in HPA.
Figure 3. TPX2 transcriptional level in subgroups of patients with HCC. (A) Boxplot showing expression level of TPX2 in normal individuals of either gender and male or female HCC patients, respectively. (B) Boxplot showing expression level of TPX2 in normal, African American, Caucasian, and Asian HCC patients. (C) Boxplot showing expression level of TPX2 in normal individuals of any age or in HCC patients aged 21-40, 41-60, 61-80, or 81â100 yr. (D) Boxplot showing expression level of TPX2 in normal individuals of any weight or in HCC patients with normal weight, extreme weight, obese or extreme obese. (E) Boxplot showing expression level of TPX2 in normal individuals or in HCC patients at stages 1, 2, 3, or 4. (F) Boxplot showing expression level of TPX2 in normal individuals or HCC patients with grade 1, 2, 3, or 4 tumors. âPâ<â.05, â Pâ<â.01, â¡Pâ<â.001.
Figure 4. The prognosis effect of TPX2 expression in HCC. (A) OS curve showing the prognostic difference between patients with high expression of TPX2 and patients with low expression of TPX2. (B) PFS curve showing the prognostic difference between patients with high expression of TPX2 and patients with low expression of TPX2. (C) PFS curve showing the prognostic difference between patients with high expression of TPX2 and patients with low expression of TPX2. (D) DSS curve showing the prognostic difference between patients with high expression of TPX2 and patients with low expression of TPX2.
Figure 5. Association analysis of TPX2 expression and infiltration levels of immune cells in HCC. TPX2 expression in HCC tissues was positively associated with tumor purity and infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs.
Figure 6. The genes coexpressed with TPX2 in HCC. (A) The global TPX2 highly associated genes identified by Pearson test in HCC cohort. (B) Heat maps showing top 50 genes positively associated with TPX2 in HCC. (C) Heat maps showing top 50 genes negatively associated with TPX2 in HCC. (D) Significantly enriched GO_BP annotations of TPX2 in HCC group. (E) Significantly enriched GO_CC annotations of TPX2 in HCC group. (F) Significantly enriched GO_MF annotations of TPX2 in HCC group. (G) Significantly enriched KEGG pathways of TPX2 in HCC group.
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