Int J Med Sci 2024; 21(2):207-218. doi:10.7150/ijms.88039 This issue Cite

Research Paper

The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma

Jin Wang1,2,3,4, Fuheng Che1,2,3,4, Yuanyuan Zhao1,2,3,4, Lai Wei1,2,3,4, Dong Chen1,2,3,4, Chen Dai1,2,3,4, Bo Zhang1,2,3,4, Xi Zhou1,2,3,4, Bo Yang1,2,3,4✉, Zhishui Chen1,2,3,4✉

1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.
3. NHC Key Laboratory of Organ Transplantation, Wuhan, China.
4. Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.

Citation:
Wang J, Che F, Zhao Y, Wei L, Chen D, Dai C, Zhang B, Zhou X, Yang B, Chen Z. The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma. Int J Med Sci 2024; 21(2):207-218. doi:10.7150/ijms.88039. https://www.medsci.org/v21p0207.htm
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Abstract

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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers. ARL-6, a member of the ADP ribosylation factor (like) (ARF) protein family, has gained attention as a potential therapeutic target in various malignancies and a prognostic biomarker. However, its specific roles in HCC, both prognostically and biochemically, remain largely unclear.

Methods: To examine the functional relevance of ARL-6 in HCC, we acquired data from GEPIA, UALCAN, TIMER, TCGA, GeneMANIA, and Metascape databases. Then, we conducted immunohistochemistry on a replication sample comprising 26 HCC specimens to assess the efficacy of the ARL-6 gene. To unravel the mechanistic intricacies, we employed diverse assays such as the cell counting kit 8 (CCK8), flow cytometry, and transwell invasion assessment.

Results: Our findings demonstrated the mRNA expression of ARL-6 was significantly upregulated in HCC compared to normal tissue, as evidenced by comprehensive database analysis. Immunohistochemistry further revealed that ARL-6 expression was remarkably higher in HCC than in para-carcinoma tissues. Moreover, ARL-6 expression exhibited noteworthy variations across diverse LIHC characteristics, including sample type, histological subtype, TP53 mutation status, nodal metastatic status, and cancer stage. In addition, high transcriptional levels of ARL-6 were correlated with diminished overall survival (OS) and disease-free survival (DFS) in HCC patients. Furthermore, our study indicated positive correlations between ARL-6 expression levels and the activities of tumor-infiltrating immune cells such as B cells, myeloid dendritic cells, macrophages, neutrophils, CD8+T cells, and CD4+T cells. Substantiating our findings, database analysis uncovered additional evidence of ARL-6 gene co-expression and its functional significance in HCC cases. Finally, we demonstrated the involvement of the ARL-6 gene in HCC cell invasion, proliferation, and apoptosis.

Conclusions: In conclusion, our investigation sheds light on the pivotal role of ARL-6 in influencing HCC prognosis and treatment by modulating the biological activities of tumor cells. These discoveries hold promise for the development of predictive biomarkers and novel therapeutic avenues for affected patients.

Keywords: hepatocellular carcinoma, ARL-6, prognostic biomarker, tumor-infiltrating immune cells


Citation styles

APA
Wang, J., Che, F., Zhao, Y., Wei, L., Chen, D., Dai, C., Zhang, B., Zhou, X., Yang, B., Chen, Z. (2024). The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma. International Journal of Medical Sciences, 21(2), 207-218. https://doi.org/10.7150/ijms.88039.

ACS
Wang, J.; Che, F.; Zhao, Y.; Wei, L.; Chen, D.; Dai, C.; Zhang, B.; Zhou, X.; Yang, B.; Chen, Z. The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma. Int. J. Med. Sci. 2024, 21 (2), 207-218. DOI: 10.7150/ijms.88039.

NLM
Wang J, Che F, Zhao Y, Wei L, Chen D, Dai C, Zhang B, Zhou X, Yang B, Chen Z. The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma. Int J Med Sci 2024; 21(2):207-218. doi:10.7150/ijms.88039. https://www.medsci.org/v21p0207.htm

CSE
Wang J, Che F, Zhao Y, Wei L, Chen D, Dai C, Zhang B, Zhou X, Yang B, Chen Z. 2024. The Prognostic and Therapeutic Roles of ARL-6 Gene in Hepatocellular Carcinoma. Int J Med Sci. 21(2):207-218.

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