Sulfiredoxin‐1 is a promising novel prognostic biomarker for hepatocellular carcinoma

Rao, Qianwen; Zhang, Shilong; Guo, Mengzhou; Yuan, Feifei; Sun, Jialei; Feng, Qi; Wang, Li‐Shun; Yang, Biwei; Xia, Jinglin

doi:10.1002/cam4.3430

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…Sulfiredoxin 1 (SRXN1) is a key factor in the antioxidant response in eukaryotic cells [ 32 ]. SRXN1 is an antioxidant enzyme that protects host cells from oxidative damage by catalysing the reduction of peroxides to reductants [ 33 ]. Studies have shown that SRXN1 is overexpressed in a variety of malignant tumours, including breast cancer [ 34 ], colorectal cancer, lung cancer, prostate cancer, and skin cancer [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer

Wang,

Yu,

Wen

et al. 2023

BMC Urol

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Purpose To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer. Methods The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients. Results A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher “GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS”, “GOBP_G2_DNA_DAMAGE_CHECKPOINT” and “GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT” GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072. Conclusions Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer

Wang,

Yu,

Wen

et al. 2023

BMC Urol

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“…Sulfiredoxin-1 (SRXN1) was revealed as a pro-tumorigenic in HCC by regulating ROS signaling 34 . In addition, SRXN1 is involved in oxidoreductase activity 35 , its overexpression may play a crucial role in the tumorigenesis and progression of HCC 36 . Nevertheless, there are not so many reports about the relationship between these genes and ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma

Luo

Yao

Xiang

et al. 2022

Sci Rep

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Ferroptosis is a novel type of cell death depending on iron and is strongly related to the development of tumors. Hepatocellular carcinoma (HCC) is a malignancy with high incidence. Despite some reports demonstrating the relation between ferroptosis-related genes and HCC, more details have not been excavated. In the present study, we collected and analyzed HCC patients' datasets from the TCGA-LIHC project and ICGC portal, respectively. Through the bioinformatic methods, we screened 126 differentially expressed genes. Then a prognostic model was established with four genes (GPX2, MT3, PRDX1, and SRXN1). PRDX1 is the hub gene of the prognosis model and has a high expression in hepatocellular carcinoma tumor tissue and cell lines. We further found that silencing PRDX1 increased the accumulation of ferrous ions and lipid peroxidation accumulation in HEPG2 cells and promoted ferroptosis in hepatocellular carcinoma. In conclusion, the study demonstrated the four-gene signature can be used to predict HCC prognosis. It also revealed the potential function of the ferroptosis-related gene PRDX1 in HCC, which can be a biomarker of the prediction for HCC outcome.

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“…Srx affects its downstream target gene hyperoxidized Prxs, transforming it to active Prxs with the presence of ATP [ 22 ]. Srx plays a critical role in tumorigenesis involved in cell proliferation, migration, and metastasis [ 23 ]. According to the previous study, Srx plays an oncogenic role in skin tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Apigenin Induced Apoptosis by Downregulating Sulfiredoxin Expression in Cutaneous Squamous Cell Carcinoma

Wang

Liu

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cutaneous squamous cell carcinoma (cSCC) is the second carcinoma in nonmelanoma skin cancer (NMSC). Sulfiredoxin (Srx) is an antioxidant protein with a role in maintaining redox homeostasis. And Srx has an oncogenic role in skin tumorigenesis. In the current study, we found that apigenin, as a natural flavonoid, downregulated the expression of Srx protein in cSCC cell lines. Apigenin also inhibited the ability of cell proliferation and migration and induced apoptosis in cSCC cell lines. Our results also showed that apigenin induced apoptosis via the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, as well as downregulated Srx expression in cSCC cell lines. Importantly, the effect of downregulation Srx by apigenin has been rescued with the inhibitor of the MAPK signaling pathway intervention. And induced apoptosis by apigenin was partially attenuated by the addition of MAPK inhibitor, Binimetinib. Our research revealed that apigenin induced apoptosis by downregulation of Srx expression through regulating the MAPK signaling pathway in cSCC cells, thus providing evidence of its applicability as a potentially effective therapeutic agent for cSCC treatment.

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Sulfiredoxin‐1 is a promising novel prognostic biomarker for hepatocellular carcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 44 publications

Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer

Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer

Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma

Apigenin Induced Apoptosis by Downregulating Sulfiredoxin Expression in Cutaneous Squamous Cell Carcinoma

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