The Correlation of HK2 Gene Expression with the Occurrence, Immune Cell Infiltration, and Prognosis of Renal Cell Carcinoma

Abstract

Objectives. Hexokinase 2 (HK2) is one of the key factors involved in the development of several human cancers. However, its role in immune cell infiltration (ICI) and tumor development in renal cell carcinoma is not yet known. Thus, we aimed to explore its relationship with ICI, overall survival, and prognosis of renal cell carcinoma. Methods. In this study, RNA-seq data from renal cancer and normal tissues were extracted from TCGA and the relationship between HK2 expression and pathological features of RCC patients was analyzed using the GEPIA and UALCAN databases. Subsequently, Western blot and qRT-PCR were performed to analyze the protein and mRNA expression of HK2 in renal cell carcinoma tissues and cell lines. Lastly, various bioinformatics tools were applied to determine the immune cell infiltration, survival, and developing prediction model. Results. The analysis of RNA-seq data revealed a high expression of HK2 in renal cell carcinoma; furthermore, Western blot and qRT-PCR also showed high expression of HK2 in renal cancer tissues and cell lines. The high expression of HK2 showed a significant positive correlation with the advanced stage of the tumor, lymph node metastasis, and worst survival in renal carcinoma patients. The high expression of HK2 was further identified as an independent risk factor of RCC patients; it also showed a significant positive immune cell infiltration RCC tumor microenvironment including macrophages, B cells, neutrophils, dendritic cells, and CD8+ T cells. Conclusion. the expression of HK2 is positively correlated with the immune cell infiltration and prognosis of renal cell carcinoma patients, thus playing an important role in renal cancer development.

Identification of the key roles of different hexokinases on the diagnosis, prognosis, tumor immunity, drug response: evidence from pan-cancer analysis and construction prognostic HKs signatures

“…Researchers have found that HKs expression is generally related to patient survival [14,15], however, Fig. 3-7 showed that direct associations varied according to the type of cancer and the member queried.…”

Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study

“…Dysregulation of lipid metabolism, driven by lipogenic genes, correlates with inferior clinical outcomes in ccRCC patients. 119 Notably, adipokines and lipid species have emerged as potential diagnostic and treatment monitoring biomarkers, and targeting fatty acid metabolism holds promise as a therapeutic strategy for ccRCC. 120 Amino acid metabolism, including glutamine, tryptophan, and arginine pathways, significantly influences tumor progression.…”

“…Furthermore, the formation of lipid droplets and dysregulated lipid metabolism constitute key features of ccRCC. Dysregulation of lipid metabolism, driven by lipogenic genes, correlates with inferior clinical outcomes in ccRCC patients 119 . Notably, adipokines and lipid species have emerged as potential diagnostic and treatment monitoring biomarkers, and targeting fatty acid metabolism holds promise as a therapeutic strategy for ccRCC 120 .…”

Metabolic reprogramming of clear cell renal cell carcinoma

“…Some literature shows that the high expression of HK2 is positively correlated with the advanced tumor, lymph node metastasis and the worst survival rate of renal cancer patients. The high expression of HK2 has been identified as an independent risk factor for RCC; It also shows a positive correlation with immune cell infiltration and prognosis in kidney cancer patients, playing an important role in the occurrence and development of cancer ( 40 ).…”