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. 2022 Jun 8:13:904114.
doi: 10.3389/fgene.2022.904114. eCollection 2022.

A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer

Sheng Liu  1 , Wenting Tang  2   3 , Jing Cao  4 , Mei Shang  1 , Hengchang Sun  1 , Jiao Gong  1 , Bo Hu  1
Affiliations

A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer

Sheng Liu et al. Front Genet. .

Erratum in

Abstract

Hepatitis A virus cellular receptor (HAVCR1) is a type-1 integral membrane glycoprotein that plays a key role in immunity and renal regeneration and is abnormally expressed in various tumor types. Nonetheless, the function of HAVCR1 in pan-cancer remains unknown. In this study, we comprehensively analyzed the expression and promoter methylation level of HAVCR1 and assessed the immune cell infiltration, correlation between stromal and immune cell admixture, CD (Cluster of Differentiation) and HAVCR1 expression and prognostic value of HAVCR1 mRNA expression in Liver hepatocellular carcinoma (LIHC) and Pancreatic adenocarcinoma (PAAD). Our results showed that HAVCR1 was overexpressed while the promoter methylation of HAVCR1 was decreased in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 was associated with increased infiltration of B cells, CD8 cells, macrophages, neutrophils and Dendritic cells in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 expression was positively correlated with the immune, stromal and estimate scores of Pancreatic adenocarcinoma and the stromal and estimate scores of Liver hepatocellular carcinoma. Furthermore, HAVCR1 expression was correlated with other immune molecules such as HHLA2 (Human endogenous retrovirus-H long terminal repeat-associating protein 2), CD44 and TNFRSF4 (TNF Receptor Superfamily Member 4) in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. During Kaplan-Meier analysis, high HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma correlated with poor survival. A marginally significant p-value (p = 0.051) was obtained when the relationship between HAVCR1 expression in Liver hepatocellular carcinoma and prognosis was analyzed, attributed to the small sample size. Overall, we provided compelling evidence that HAVCR1 could be a prognostic and diagnostic marker for Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.

Keywords: diagnostic; havcr1; liver hepatocellular carcinoma; pancreatic adenocarcinoma; prognosis.

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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
Workflow chart for this study.
FIGURE 2
FIGURE 2
HAVCR1 was overexpressed in tumor tissues compared to normal tissue in Pan-cancer. (A) HAVCR1 was aberrantly expressed in numerous tumors and was upregulated in most tumors. (B,C) HAVCR1 mRNA expression in tumor and normal tissue in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. (D,E) HAVCR1 mRNA expression in tumor and normal tissue in different stages of Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. (F,G) Promoter methylation levels of HAVCR1 were mostly decreased in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ****p < 0.001.
FIGURE 3
FIGURE 3
The OS curve of HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. (A,B) Database Analysis The correlation between HAVCR1 expression and survival in pancreatic cancer was analyzed by Kaplan-Meier plotter; HAVCR1 overexpression was associated with a poor prognosis in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.
FIGURE 4
FIGURE 4
Analysis of the relationship between immune cells infiltration and HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. (A) TIMER2.0 was used to analyze the expression level of HAVCR1 in immune cells, including B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil cell and dendritic cell. High HAVCR1 expression correlated with immune cell infiltration in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. (B) Correlation of scores in patients with HAVCR1 in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma, stromal and immune cell admixture from expression data correlated to HAVCR1 expression. p values <0.05 were statistically significant.
FIGURE 5
FIGURE 5
HAVCR1 is correlated with other checkpoints in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. Correlation between HAVCR1 and marker gene sets of immune cells across cancers in TCGA. Our results showed that HHLA2, CD44 and TNFSF4 were correlated with HAVCR1 expression in Liver hepatocellular carcinoma (A) and Pancreatic adenocarcinoma (B).
FIGURE 6
FIGURE 6
The ROC curve of HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.The ROC curves were used to evaluate the predictive power of the HAVCR1 of 5-years survival in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. The AUC of the ROC curve was 0.738 in Liver hepatocellular carcinoma (A) and 0.619 in Pancreatic adenocarcinoma (B).
FIGURE 7
FIGURE 7
Representative images of HAVCR1 expression in Liver hepatocellular carcinoma by IHC. Representative images of HAVCR1 expression in normal tissue (A) and Liver hepatocellular carcinoma tissues (B–F) captured by a Nikon microscope. The scale bar is 100 μm.
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