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  • Hindawi Limited  (3)
  • Ruan, Yajun  (3)
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  • Hindawi Limited  (3)
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  • 1
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-11-11), p. 1-28
    Abstract: Redox homeostasis is the key to cell survival, and its imbalance can promote the occurrence and progression of tumors. However, it remains unclear whether these redox-related genes (RRGs) have potential roles in the tumor microenvironment, immunotherapy, and drug sensitivity. Here, we performed a systematic and comprehensive analysis of 489 prostate cancer (PC) samples from The Cancer Genome Atlas database and 214 PC samples from 8 datasets in the Gene Expression Omnibus database to determine redox modification patterns and the redox scoring system for PC. We identified two modification patterns (Redox_A and Redox_B) in PC using unsupervised consensus clustering based on 1410 differential expression RRGs. We then compared the prognostic value, tumor microenvironment characteristics, immune cell infiltration, and molecular characteristics of the two patterns. The Redox_A pattern was significantly enriched in the carcinogenic activation signaling pathways and had a poor prognosis, while the Redox_B pattern was mainly enriched in a variety of metabolic and redox pathways and had a good prognosis. Next, redox-related characteristic genes were extracted from these two patterns, and a scoring system (Redox_score) was constructed to evaluate PC patients. Further analysis indicated that lower Redox_score patients had a better prognosis, while higher Redox_score patients had a higher tumor mutation burden, driver gene mutation rate, and immune checkpoint inhibitor gene expression. We also found that higher Redox_score patients were more responsive to anti-PD-1 immunotherapy. Moreover, Redox_score was determined to be significantly correlated with anticancer drug sensitivity and resistance. Our study provides a comprehensive analysis of redox modifications in PC and reveals new patterns of PC based on RRGs, which will provide insights into the complex mechanisms of PC and develop more effective individualized therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2455981-7
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  • 2
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-11-24), p. 1-32
    Abstract: Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2455981-7
    Location Call Number Limitation Availability
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  • 3
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-4-21), p. 1-35
    Abstract: The imbalance of the redox system has been shown to be closely related to the occurrence and progression of many cancers. However, the biological function and clinical significance of redox-related genes (RRGs) in clear cell renal cell carcinoma (ccRCC) are unclear. In our current study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database of ccRCC patients and identified the differential expression of RRGs in tumor and normal kidney tissues. Then, we identified a total of 344 differentially expressed RRGs, including 234 upregulated and 110 downregulated RRGs. Fourteen prognosis-related RRGs (ADAM8, CGN, EIF4EBP1, FOXM1, G6PC, HAMP, HTR2C, ITIH4, LTB4R, MMP3, PLG, PRKCG, SAA1, and VWF) were selected out, and a prognosis-related signature was constructed based on these RRGs. Survival analysis showed that overall survival was lower in the high-risk group than in the low-risk group. The area under the receiver operating characteristic curve of the risk score signature was 0.728 at three years and 0.759 at five years in the TCGA cohort and 0.804 at three years and 0.829 at five years in the E-MTAB-1980 cohort, showing good predictive performance. In addition, we explored the regulatory relationships of these RRGs with upstream miRNA, their biological functions and molecular mechanisms, and their relationship with immune cell infiltration. We also established a nomogram based on these prognostic RRGs and performed internal and external validation in the TCGA and E-MTAB-1980 cohorts, respectively, showing an accurate prediction of ccRCC prognosis. Moreover, a stratified analysis showed a significant correlation between the prognostic signature and ccRCC progression.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2455981-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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