Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds
This study aimed to explore clinical significance of interleukin-1 receptor-associated kinase 1 (IRAK1) in the diagnosis, prognosis, and targeted therapy of hepatocellular carcinoma. A systematic analysis based on the cancer genome atlas (TCGA) indicated that IRAK1 was highly expressed in 18 cancer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/29/11/700 |
| _version_ | 1797465593038766080 |
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| author | Chaoying Song Xinyu Gu Ruifang Li |
| author_facet | Chaoying Song Xinyu Gu Ruifang Li |
| author_sort | Chaoying Song |
| collection | DOAJ |
| description | This study aimed to explore clinical significance of interleukin-1 receptor-associated kinase 1 (IRAK1) in the diagnosis, prognosis, and targeted therapy of hepatocellular carcinoma. A systematic analysis based on the cancer genome atlas (TCGA) indicated that IRAK1 was highly expressed in 18 cancer types (<i>p</i> < 0.01) and may be a pan-cancer biomarker. In hepatocellular carcinoma, the alteration rate of IRAK1 was rather high (62.4%), in which mRNA high relative to normal predominated (58.9%). Higher expression was associated with shorter overall survival (<i>p</i> < 0.01). IRAK1 expression correlated positively with pathology stage and tumor grade (for the latter there was only a slight trend). Interestingly, it correlated positively with TP53 mutation (<i>p</i> < 0.001), suggesting a possible strategy for targeting TP53 via IRAK1. Immunohistochemistry experiments confirmed a higher positive rate of IRAK1 in carcinoma than in para-carcinoma tissues (χ<sup>2</sup> = 18.006, <i>p</i> < 0.001). Higher tumor grade correlated with more strongly positive staining. Molecular docking revealed cryptotanshinone, matrine, and harmine as the best hit compounds with inhibition potential for IRAK1. Our findings suggest that IRAK1 may play biologically predictive roles in hepatocellular carcinoma. The suppression of IRAK1/NF-κB signaling via inhibition of IRAK1 by the hit compounds can be a potential strategy for the targeted therapy. |
| first_indexed | 2024-03-09T18:24:45Z |
| format | Article |
| id | doaj.art-b7ac02d62a2b4407a70231da9de10ae4 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-09T18:24:45Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-b7ac02d62a2b4407a70231da9de10ae42023-11-24T08:03:27ZengMDPI AGCurrent Oncology1198-00521718-77292022-11-0129118904891610.3390/curroncol29110700Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural CompoundsChaoying Song0Xinyu Gu1Ruifang Li2Department of Pharmaceutical Sciences, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, ChinaDepartment of Pharmaceutical Sciences, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, ChinaDepartment of Pharmaceutical Sciences, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, ChinaThis study aimed to explore clinical significance of interleukin-1 receptor-associated kinase 1 (IRAK1) in the diagnosis, prognosis, and targeted therapy of hepatocellular carcinoma. A systematic analysis based on the cancer genome atlas (TCGA) indicated that IRAK1 was highly expressed in 18 cancer types (<i>p</i> < 0.01) and may be a pan-cancer biomarker. In hepatocellular carcinoma, the alteration rate of IRAK1 was rather high (62.4%), in which mRNA high relative to normal predominated (58.9%). Higher expression was associated with shorter overall survival (<i>p</i> < 0.01). IRAK1 expression correlated positively with pathology stage and tumor grade (for the latter there was only a slight trend). Interestingly, it correlated positively with TP53 mutation (<i>p</i> < 0.001), suggesting a possible strategy for targeting TP53 via IRAK1. Immunohistochemistry experiments confirmed a higher positive rate of IRAK1 in carcinoma than in para-carcinoma tissues (χ<sup>2</sup> = 18.006, <i>p</i> < 0.001). Higher tumor grade correlated with more strongly positive staining. Molecular docking revealed cryptotanshinone, matrine, and harmine as the best hit compounds with inhibition potential for IRAK1. Our findings suggest that IRAK1 may play biologically predictive roles in hepatocellular carcinoma. The suppression of IRAK1/NF-κB signaling via inhibition of IRAK1 by the hit compounds can be a potential strategy for the targeted therapy.https://www.mdpi.com/1718-7729/29/11/700IRAK1hepatocellular carcinomaTP53 mutationtargeted therapyIRAK1/NF-κB signalingnatural compound |
| spellingShingle | Chaoying Song Xinyu Gu Ruifang Li Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds Current Oncology IRAK1 hepatocellular carcinoma TP53 mutation targeted therapy IRAK1/NF-κB signaling natural compound |
| title | Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds |
| title_full | Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds |
| title_fullStr | Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds |
| title_full_unstemmed | Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds |
| title_short | Expression of IRAK1 in Hepatocellular Carcinoma, Its Clinical Significance, and Docking Characteristics with Selected Natural Compounds |
| title_sort | expression of irak1 in hepatocellular carcinoma its clinical significance and docking characteristics with selected natural compounds |
| topic | IRAK1 hepatocellular carcinoma TP53 mutation targeted therapy IRAK1/NF-κB signaling natural compound |
| url | https://www.mdpi.com/1718-7729/29/11/700 |
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