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.
Highlights
Renal cell carcinoma (RCC) is the malignancy of the proximal tubular epithelial cells of the kidney, covering up to 90% of the primary renal malignancies [1]
HK has two isoforms HK1 and Hexokinase 2 (HK2); the former is widely expressed in adult normal tissues, and the latter is overexpressed in a variety of cancers including renal cell carcinoma [15]
Our results revealed that the expression of HK2, lymph node metastasis, and tumor stage was significantly correlated with the OS rate of RCC patients in univariate analysis (Table 2)
Summary
Renal cell carcinoma (RCC) is the malignancy of the proximal tubular epithelial cells of the kidney, covering up to 90% of the primary renal malignancies [1]. Based on the tumor tissue classification, it has been divided into kidney clear cell carcinoma, papillary carcinoma, and chromophobe cell cancer [4]. The reason for the high frequency of renal cancer is a lack of specific clinical manifestations and features at the early stage; most cases (20–30%) at the time of initial diagnosis showed metastasis [5]. Since the pathogenesis of renal cancer is still unclear, it is necessary to find new potential underlying factors involved in the development and progression of RCC. The upregulation of HK2 in cancers is mainly associated with tumor progression and mortality [13]. The high expression of HK2 has been associated with drug resistance and metastasis in Disease Markers various cancers [14], making HK2 a potential anticancer therapeutic target
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