Dataset Information

Using Genomic and Transcriptome Analyses to Identify the Role of the Oxidative Stress Pathway in Renal Clear Cell Carcinoma and Its Potential Therapeutic Significance

ABSTRACT: Oxidative stress (OS) refers to endogenous and/or exogenous stimulation when the balance between oxidation and antioxidants in the body is disrupted, resulting in excessive production of free radicals. Excessive free radicals exert a series of negative effects on the body, which can result in the oxidation of and infliction of damage on biological molecules and further cause cell death and tissue damage, which are related to many pathological processes. Pathways related to OS have always been the focus of medical research. Several studies are being conducted to develop strategies to treat cancer by exploring the OS pathways. Therefore, this study is aimed at determining the correlation between the OS pathway and kidney renal clear cell carcinoma (KIRC) through bioinformatics analysis, at proving the effect of common anticancer drugs on the OS pathway, and at constructing a prognosis model of patients with KIRC based on several genes with the strongest correlation between the OS pathway and KIRC. We first collected and analyzed gene expression and clinical information of related patients through TCGA database. Then, we divided the samples into three clusters according to their gene expression levels obtained through cluster analysis. Using these three clusters, we performed GDSC drug analysis and GSEA analysis and examined the correlation among the OS pathway, histone modification, and immune cell infiltration. We also analyzed the response of anti-PD-1 and anti-CTLA-4 to the OS pathway. Thereafter, we used LASSO regression to select the most suitable nine genes, combined with the clinicopathological characteristics to establish the prognosis model of patients with KIRC, and verified the scientific precision of the model. Finally, tumor mutational burden was calculated to verify whether patients would benefit from immunotherapy. The results of this study may provide a reference for the establishment of treatment strategies for patients with KIRC.

SUBMITTER: Che X

PROVIDER: S-EPMC8550864 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundRenal cell carcinoma (RCC) is a fatal disease, in which the PI3K/AKT/mTOR signaling pathway serves an important role in the tumorigenesis. Previous studies have reported the prognostic significance of PI3K/AKT/mTOR signaling pathway members in RCC; however, there is insufficient evidence to date to confirm this. Thus, the present study aimed to systematically investigate the prognostic roles of multiple PI3K/AKT/mTOR signaling proteins in clear cell RCC (ccRCC) using online large-scale databases.MethodsThe mRNA expression profiles of PI3K/AKT/mTOR signaling pathway proteins PTEN, PIK3CA, PIK3CB, PIK3CD, PIK3CG, AKT1, AKT2, AKT3 and mTOR were investigated using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases, and the protein expression levels of PI3K, AKT and mTOR were detected using western blotting (WB) analysis. In addition, the correlation between mRNA or protein expression levels and the prognostic significance was analyzed using the Kaplan-Meier (K-M) plotter (n = 530), the Human Protein Atlas (HPA; n = 528) and The Cancer Protein Atlas (TCPA; n = 445) databases.ResultsThe GEPIA revealed that the mRNA expression of major PI3K/AKT/mTOR pathway members, including PTEN, PIK3CA, PIK3CB, AKT1, AKT2 and AKT3, were negatively correlated with ccRCC stages (P < 0.05), though most of their mRNA and protein expression levels were notsignificantly different between ccRCC and normal tissues using GEPIA, Oncomine and WB analyses (P < 0.05). Meanwhile, using the K-M plotter and HPA prognostic analysis, it was found that the mRNA expression levels of the majority of the PI3K/AKT/mTOR signaling pathway members, including PTEN, PIK3CA, PIK3CB, PIK3CG, AKT3 and mTOR were positively correlated with overall survival (OS), whereas PIK3CD mRNA expression was negatively correlated with OS (P < 0.05). Furthermore, TCPA prognostic analysis observed that several of the key molecules of the PI3K/AKT/mTOR signaling pathway [PTEN, p-AKT (S473) and p-mTOR (S2448)] were also positively correlated with OS in patients with ccRCC (P < 0.05). In conclusion, the present study suggested that several members of the PI3K/AKT/mTOR signaling pathway, especially PTEN, may be favorable prognostic factors in ccRCC, which indicated that the PI3K/AKT/mTOR signaling pathway may be implicated in ccRCC initiation and progression.

Dataset Information

Using Genomic and Transcriptome Analyses to Identify the Role of the Oxidative Stress Pathway in Renal Clear Cell Carcinoma and Its Potential Therapeutic Significance

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets