A novel gene signature related to oxidative stress predicts the prognosis in clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (UCN) was chosen for further study; some necessary vitro experiments proved that the UCN could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. UCN played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.

A novel oxidative stress-related genes signature associated with clinical prognosis and immunotherapy responses in clear cell renal cell carcinoma

“…A recent article by Ma et al also reported that an oxidative stress signature predicted clinical outcome in ccRCC and 4 oxidative stress genes (UCN, PLG, FOXM1, HRH2) were selected to construct a prognostic signature (64). The AUC of the 4 oxidative stress genes prognostic signature was 0.77 at 1 year, 0.70 at 3 years, and 0.71 at 5 years in the TCGA.…”

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…For instance, activating transcription factor 3 (ATF3 were correlated with RCC progression [28], genes ABCB1, AGER, E2F1, FOXM1, HADH ISG15, KCNMA1, PLG, and TEK were correlated with the clinical outcome and immune status of ccRCC patients [27], genes UCN, PLG, FOXM1, and HRH2 were associated with the ccRCC prognosis [29], long non-coding RNAs (lncRNA) SPART-AS1, AL162586.1 Based on bioinformatic analysis, several current studies have identified sets of genes related to oxidative stress (ORG). For instance, activating transcription factor 3 (ATF3) were correlated with RCC progression [28], genes ABCB1, AGER, E2F1, FOXM1, HADH, ISG15, KCNMA1, PLG, and TEK were correlated with the clinical outcome and immune status of ccRCC patients [27], genes UCN, PLG, FOXM1, and HRH2 were associated with the ccRCC prognosis [29], long non-coding RNAs (lncRNA) SPART-AS1, AL162586.1, LINC00944, LINC01550, HOXB-AS4, LINC02027, and DOCK9-DT were associated with ccRCC aggressiveness [30,31], mitochondrial genes ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR were linked to the ccRCC prognosis [12], and genes ADAM8, CGN, EIF4EBP1, FOXM1, G6PC, HAMP, HTR2C, ITIH4, LTB4R, MMP3, PLG, PRKCG, SAA1, and VWF, and microRNAs related to the redox status and ccRCC progression [12], were found to be essential for the response to oxidative stress. Recently, a transcription factor for the oxidative stress response, broad complex-tramtrack-bric-a-brac and cap 'n' collar homology 1 (BACH1), has been labeled an essential factor involved in RCC progression in vivo [32].…”

Construction of an oxidative stress-associated genes signature in breast cancer by machine learning algorithms

“…7 A four oxidative stress gene signature was constructed to predict survival in clear cell renal cell carcinoma. 8 With the escalating prominence of oxidative stress in breast cancer research, the exploration of prognostic factors associated with oxidative stress in the development and progression of breast cancer has emerged as a focal point of investigation. A previous study constructed an oxidative stress long noncoding RNA prognostic signature for breast cancer and proved that it is closely related to the tumour microenvironment.…”