AUTHOR=Liu Shanshan , Zhao Wei , Li Xuemei , Zhang La , Gao Yu , Peng Qiling , Du Chengyou , Jiang Ning 

TITLE=AGTRAP Is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.713017

DOI=10.3389/fonc.2021.713017

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Recently, it has been reported that angiotensin II receptor-associated protein (<italic>AGTRAP</italic>) plays a substantial role in tumor progression. Nevertheless, the possible role of <italic>AGTRAP</italic> in hepatocellular carcinoma (HCC) remains unrecognized.</p></sec><sec><title>Methods</title><p>The metabolic gene rapid visualizer, Cancer Cell Line Encyclopedia, Human Protein Atlas, and Hepatocellular Carcinoma Database were used to analyze the expression of <italic>AGTRAP</italic> in HCC tissues and normal liver tissues or adjacent tissues. Kaplan-Meier plotter and UALCAN analysis were used to assess the prognostic and diagnostic value of <italic>AGTRAP.</italic> LinkedOmics and cBioPortal were used to explore the genes co-expressed with <italic>AGTRAP</italic> in HCC. To further understand the potential mechanism of <italic>AGTRAP</italic> in HCC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were performed using <italic>R</italic> software, the protein-protein interaction (PPI) network was established using the STRING database, and the immune infiltration and T-cell exhaustion related to <italic>AGTRAP</italic> were explored <italic>via</italic> Timer and GEPIA. In addition, immunohistochemistry was used to detect the expression of AGTRAP protein in HCC tissues and paired adjacent tissues from clinical specimens.</p></sec><sec><title>Results</title><p>This study found that the mRNA and protein levels of AGTRAP in HCC tissues were higher than those in normal liver tissues and adjacent tissues, and higher mRNA levels of <italic>AGTRAP</italic> were associated with higher histological grade and a poor overall survival in HCC patients. The area under the receiver operating characteristic curve (AUC) of <italic>AGTRAP</italic> was 0.856, suggesting that it could be a diagnostic marker for HCC. Moreover, the alteration rate of <italic>AGTRAP</italic> in HCC was 8%, and <italic>AGTRAP</italic> was involved in HCC probably through the NF-κB and MAPK signaling pathways. Furthermore, <italic>AGTRAP</italic> was positively correlated with the infiltration of CD8<sup>+</sup> T cells, CD4<sup>+</sup> T cells, B cells, macrophages, dendritic cells, and neutrophils, and the levels of <italic>AGTRAP</italic> were significantly correlated with T-cell exhaustion biomarkers. The immunohistochemistry results confirmed that the protein levels of AGTRAP were consistently higher in HCC tissues than in paired adjacent tissues.</p></sec><sec><title>Conclusion</title><p>The clinical value of <italic>AGTRAP</italic> and its correlation with immune infiltration in HCC was effectively identified in clinical data from multiple recognized databases. These findings indicate that <italic>AGTRAP</italic> could serve as a potential biomarker in the treatment of HCC, thereby informing its prognosis, diagnosis, and even immunotherapy.</p></sec>