Integrated Analysis of the Roles of Oxidative stress related genes and Prognostic Value in Clear Cell Renal Cell Carcinoma

Abstract Background ：As the most common diagnosed subtype in renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) patients suffer from the threat of tumor metastasis and recrudesce. Previous research has established that oxidative stress could induce tumorigenesis in many cancers and can be a cancer therapeutic target. Despite these, little progress has been made in the association of oxidative stress related genes (OSRGs) with ccRCC. Methods： MTT survival assay, qRT-PCR, apoptosis assay, cell cycle assay, ROS assay, IHC staining, were used in vitro experiments. Results： In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) relevant to overall survival (OS) were screened, as well as their mutual regulatory networks were structured by data from the TCGA database. Moreover, we constructed the risk model of the OSRGs, and performed clinical prognostic analysis and validation. Next, we correlated MELK, PYCR1, and PML with immune infiltration in ccRCC. Tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, cellular experiment in vitro demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing G1 phase cycle arrest. The intracellular ROS levels were elevated after knockdown of the two genes. Consulsion: Our results presented a potential application of DEORGs in prognostic prediction for ccRCC and identified two biomarkers named PYCR1 and MELK, which could regulate the proliferation of ccRCC by affecting the ROS levels. Further, PYCR1 and MELK could be promising to predict the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.