Zhihui Tian,1 Yan Guo,2 Rong Yang,1 Wenhui Yang1 

1Department of Gastroenterology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan City, Shanxi Province, 030013, People’s Republic of China; 2Department of Good Clinical Practice Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan City, Shanxi Province, 030013, People’s Republic of China

Correspondence: Rong Yang; Wenhui Yang, Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, No. 3, Staff New Street, Xinghualing District, Taiyuan City, Shanxi Province, 030000, People’s Republic of China, Email wbbyr2005@163.com; yangwenhui10012@163.com

Background: The tumor immune microenvironment (TME) plays a key role in the development of hepatocellular carcinoma (HCC). As the important components of TME, interleukin-2 (IL-2) mediates immune responses by specifically binding to the interleukin-2 receptor (IL-2R). This study aimed to explore the role of IL-2R in HCC development and provided possible clinical implications in HCC prognosis and treatment.
Methods: The IL-2R genetic data were acquired from publicly available TCGA and CCLE databases. Data processing and analysis, including construction of the prognostic model and evaluation of immune status in HCC, were performed on Xiantao platform by using statistical methods including the Wilcoxon test, Cox regression analysis, correlation analysis. GEPIA2 was used to explore the relationship between IL-2R genes expression and clinical stages, while genetic variations in IL-2R subunits in HCC were determined using cBioPortal. The IL-2Rα co-expression gene analysis was conducted on the LinkedOmics database. Enzyme-linked immunosorbent assay (ELISA), colorimetric method, and flow cytometric method were used to analyze peripheral blood samples from patients with HCC.
Results: A prognostic risk model was established by incorporating IL-2Rα, IL-2Rβ, and IL-2Rγ expression. The infiltration levels of B cell memory, T cell regulatory cells (Tregs), and immune checkpoints (PDCD1, CTLA4, CD274 and TIGIT) were significantly elevated in high-risk group of the risk model. Additionally, sIL-2Rα levels were positively correlated with tumor-specific growth factor (TSGF) and Tregs in the peripheral blood of HCC patients.
Conclusion: The prognostic risk model based on IL-2R subunits may play a role in the regulation of immune function within the HCC tumor microenvironment. Besides, IL-2Rα may act as a more important role in HCC development among the three IL-2R subunits. Further research will be needed to verify these initial findings. Overall, these results may provide important insights in clinical prognosis and therapeutic strategies for HCC.

Keywords: HCC, hepatocellular carcinoma, IL-2R, tumor microenvironment, prognosis, bioinformatics