Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy
To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The m...
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2196 |
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| author | Hui-Zhou Li Qing-Qing Liu De-Hua Chang Shu-Xian Li Long-Tao Yang Peng Zhou Jiang-Bei Deng Chang-Hao Huang Yu-Dong Xiao |
| author_facet | Hui-Zhou Li Qing-Qing Liu De-Hua Chang Shu-Xian Li Long-Tao Yang Peng Zhou Jiang-Bei Deng Chang-Hao Huang Yu-Dong Xiao |
| author_sort | Hui-Zhou Li |
| collection | DOAJ |
| description | To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial–mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-11T00:06:28Z |
| publishDate | 2023-08-01 |
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| series | Biomedicines |
| spelling | doaj.art-60c0ee715fbd43b28250583b2cbc2bc92023-11-19T00:20:45ZengMDPI AGBiomedicines2227-90592023-08-01118219610.3390/biomedicines11082196Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib TherapyHui-Zhou Li0Qing-Qing Liu1De-Hua Chang2Shu-Xian Li3Long-Tao Yang4Peng Zhou5Jiang-Bei Deng6Chang-Hao Huang7Yu-Dong Xiao8Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Diagnostic and Interventional Radiology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Intervention, Changsha Central Hospital, University of South Chian, Changsha 410011, ChinaThe Hunan Provincial Key Laboratory of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaTo improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial–mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.https://www.mdpi.com/2227-9059/11/8/2196hepatocellular carcinomaNOX4epithelial–mesenchymal transitionsorafenib resistance |
| spellingShingle | Hui-Zhou Li Qing-Qing Liu De-Hua Chang Shu-Xian Li Long-Tao Yang Peng Zhou Jiang-Bei Deng Chang-Hao Huang Yu-Dong Xiao Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy Biomedicines hepatocellular carcinoma NOX4 epithelial–mesenchymal transition sorafenib resistance |
| title | Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy |
| title_full | Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy |
| title_fullStr | Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy |
| title_full_unstemmed | Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy |
| title_short | Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy |
| title_sort | identification of nox4 as a new biomarker in hepatocellular carcinoma and its effect on sorafenib therapy |
| topic | hepatocellular carcinoma NOX4 epithelial–mesenchymal transition sorafenib resistance |
| url | https://www.mdpi.com/2227-9059/11/8/2196 |
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