CYP2J2 Is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma

Abstract

Cytochrome P450 family 2 subfamily J member 2 (CYP2J2), a member of the monooxygenase cytochrome P450 (CYP) family and the only member of the human CYP2J subfamily, has many functions, including regulation of oxidative stress, inflammation, apoptosis, and immune responses. However, its role in cancer development has not been clearly elucidated. In this study, expression levels of CYP2J2 in various cancer types were determined using the Oncomine, the Gene Expression Profiling Interactive Analysis (GEIPA), DriverDBv3, UALCAN, and Tumor Immune Estimation Resource (TIMER) databases. The prognostic value of CYP2J2 for KIRC was analyzed using GEPIA, UALCAN, OSkirc, and DriverDBv3 databases. We evaluated the expression levels of CYP2J2 transcript, protein, and promoter methylation at different clinical characteristics in KIRC through the UALCAN database. Simultaneously, CYP2J2 network-related functions were evaluated using the GeneMANIA interactive tool while the biological processes involved in CYP2J2 and its interactive genes were investigated through Metascape and FunRich. Then, we used TIMER to determine the correlation between CYP2J2 expression levels and immune infiltration levels in KIRC. In KIRC, the CYP2J2 gene, RNA, and protein were found to be overexpressed. However, the methylation level of CYP2J2 promoter in KIRC was lower than in normal tissues. Surprisingly, elevated expression levels of CYP2J2 exhibited better prognostic outcomes in KIRC. Evaluation of protein-protein interaction networks and biological processes revealed that CYP2J2 was principally involved in immune responses, apoptosis, and other metabolic processes. Moreover, we found that the expression levels of CYP2J2 were positively correlated with infiltration levels of B cells, CD8 + T cells, neutrophils, and dendritic cells in KIRC. Therefore, we speculated that the overexpression of CYP2J2 prolonged the survival outcome of KIRC patients, which may be related to the change of tumor immune microenvironment. Moreover, all these new understandings of CYP2J2 may provide important value for the early diagnosis and new targeted drug therapy of KIRC.

Toll-Like Receptors Serve as Biomarkers for Early Diagnosis and Prognosis Assessment of Kidney Renal Clear Cell Carcinoma by Influencing the Immune Microenvironment: Comprehensive Bioinformatics Analysis Combined With Experimental Validation

“…Renal cell carcinoma (RCC) can be divided into different subtypes according to its histological characteristics with unique genetic and molecular alterations, different clinical processes and therapeutic responses (Linehan et al, 2010;Linehan and Ricketts, 2013;Moch et al, 2016). RCC is a tumor originating from renal epithelium (Sanchez-Gastaldo et al, 2017;Zou and Mo, 2021). The most common pathological subtype of RCC is kidney renal clear cell carcinoma (KIRC), accounting for about 75% of RCC (Linehan and Ricketts, 2019).…”

Acetylshikonin, A Novel CYP2J2 Inhibitor, Induces Apoptosis in RCC Cells via FOXO3 Activation and ROS Elevation

“…The former studies identified that CYP2J2 expressions are particularly high in extrahepatic tissues, including the heart, pancreas, lung, kidney, brain, and skeletal muscle [ 36 , 37 ]. Especially, the recent study elucidated that CYP2J2 can be used as a biomarker in renal clear cell carcinoma [ 38 ]. The CYP2J2 are found to have strong and selective upregulated expressions in human tumor cells [ 39 ] and had a protective effect against ROS-induced cell deaths in adult ventricular myocytes and breast cancer MDA-MB-468 cells [ 40 , 41 ].…”

Identification of Survival Risk and Immune-Related Characteristics of Kidney Renal Clear Cell Carcinoma

“…It is important to analyze the clinicopathological features of KIRC patients according to the WHO classification and Tumor Node Metastasis (TNM) staging for selecting appropriate treatment methods [ 6 ]. However, there may be significant differences in prognosis even in patients with the same TNM staging and pathological grade after similar treatment [ 7 , 8 ], indicating that KIRC is a heterogeneous tumor, and the existing clinicopathological features and classification are not sufficient to evaluate the prognosis and risk stratification of KIRC patients. Therefore, finding a new method with high predictive value is of great significance to improve the prognosis of KIRC.…”