Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma
Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in a...
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| Veröffentlicht in: | Translational research : the journal of laboratory and clinical medicine 2020-09, Vol.223, p.1-14 |
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| creator | Kaushik, Dharam Ashcraft, Keith A. Wang, Hanzhang Shanmugasundaram, Karthigayan Shah, Pankil K. Gonzalez, Gabriela Nazarullah, Alia Tye, Cooper B. Liss, Michael A. Pruthi, Deepak K. Mansour, Ahmed M. Chowdhury, Wasim Bacich, Dean Zhang, Hao Watson, Amanda L. Block, Karen O'Keefe, Denise Rodriguez, Ronald |
| description | Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC. |
| doi_str_mv | 10.1016/j.trsl.2020.05.009 |
| format | Article |
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However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.</description><identifier>ISSN: 1931-5244</identifier><identifier>EISSN: 1878-1810</identifier><identifier>DOI: 10.1016/j.trsl.2020.05.009</identifier><identifier>PMID: 32492552</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Carcinoma, Renal Cell - enzymology ; Carcinoma, Renal Cell - pathology ; Cell Line, Tumor ; Cell Nucleus - enzymology ; Disease Progression ; Female ; Humans ; Kaplan-Meier Estimate ; Kidney Neoplasms - enzymology ; Kidney Neoplasms - pathology ; Male ; Middle Aged ; Multivariate Analysis ; NADPH Oxidase 4 - metabolism ; Progression-Free Survival</subject><ispartof>Translational research : the journal of laboratory and clinical medicine, 2020-09, Vol.223, p.1-14</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-4144f3d73a1dc2bb350bfbc4ba246a455cbee322a0d8d9bf2f6f28cfb158c1c43</citedby><cites>FETCH-LOGICAL-c455t-4144f3d73a1dc2bb350bfbc4ba246a455cbee322a0d8d9bf2f6f28cfb158c1c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.trsl.2020.05.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32492552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaushik, Dharam</creatorcontrib><creatorcontrib>Ashcraft, Keith A.</creatorcontrib><creatorcontrib>Wang, Hanzhang</creatorcontrib><creatorcontrib>Shanmugasundaram, Karthigayan</creatorcontrib><creatorcontrib>Shah, Pankil K.</creatorcontrib><creatorcontrib>Gonzalez, Gabriela</creatorcontrib><creatorcontrib>Nazarullah, Alia</creatorcontrib><creatorcontrib>Tye, Cooper B.</creatorcontrib><creatorcontrib>Liss, Michael A.</creatorcontrib><creatorcontrib>Pruthi, Deepak K.</creatorcontrib><creatorcontrib>Mansour, Ahmed M.</creatorcontrib><creatorcontrib>Chowdhury, Wasim</creatorcontrib><creatorcontrib>Bacich, Dean</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Watson, Amanda L.</creatorcontrib><creatorcontrib>Block, Karen</creatorcontrib><creatorcontrib>O'Keefe, Denise</creatorcontrib><creatorcontrib>Rodriguez, Ronald</creatorcontrib><title>Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma</title><title>Translational research : the journal of laboratory and clinical medicine</title><addtitle>Transl Res</addtitle><description>Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.</description><subject>Carcinoma, Renal Cell - enzymology</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - enzymology</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney Neoplasms - enzymology</subject><subject>Kidney Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>NADPH Oxidase 4 - metabolism</subject><subject>Progression-Free Survival</subject><issn>1931-5244</issn><issn>1878-1810</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUlLBDEQhYMo7n_Ag-TopdusPd0ggowriArqOWSp1gw9nTHpcfn3ZhgVvXhJAu-rV5V6CO1RUlJCq8NJOcTUlYwwUhJZEtKsoE1aj-qC1pSs5nfDaSGZEBtoK6UJIaJqiFhHG5yJhknJNtH9zdx2oCO-OTm9u8Th3TudoBBYpxSs1wM4_OaHZ-x8gqzgWQxPEVLyoce-xxF63WELXT50tL4PU72D1lrdJdj9urfR4_nZw_iyuL69uBqfXBdWSDkUggrRcjfimjrLjOGSmNZYYTQTlc6INQCcMU1c7RrTsrZqWW1bQ2VtqRV8Gx0vfWdzMwVnoR-i7tQs-qmOHypor_4qvX9WT-FV1ZTSqhllg4Mvgxhe5pAGNfVp8RfdQ5gnxQRpKlHxhmeULVEbQ0oR2p82lKhFGmqiFmmoRRqKSJXTyEX7vwf8KflefwaOlgDkNb16iCpZD70F5yPYQbng__P_BMA1ncg</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Kaushik, Dharam</creator><creator>Ashcraft, Keith A.</creator><creator>Wang, Hanzhang</creator><creator>Shanmugasundaram, Karthigayan</creator><creator>Shah, Pankil K.</creator><creator>Gonzalez, Gabriela</creator><creator>Nazarullah, Alia</creator><creator>Tye, Cooper B.</creator><creator>Liss, Michael A.</creator><creator>Pruthi, Deepak K.</creator><creator>Mansour, Ahmed M.</creator><creator>Chowdhury, Wasim</creator><creator>Bacich, Dean</creator><creator>Zhang, Hao</creator><creator>Watson, Amanda L.</creator><creator>Block, Karen</creator><creator>O'Keefe, Denise</creator><creator>Rodriguez, Ronald</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200901</creationdate><title>Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma</title><author>Kaushik, Dharam ; 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However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32492552</pmid><doi>10.1016/j.trsl.2020.05.009</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Translational research : the journal of laboratory and clinical medicine, 2020-09, Vol.223, p.1-14 |
| issn | 1931-5244 1878-1810 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Carcinoma, Renal Cell - enzymology Carcinoma, Renal Cell - pathology Cell Line, Tumor Cell Nucleus - enzymology Disease Progression Female Humans Kaplan-Meier Estimate Kidney Neoplasms - enzymology Kidney Neoplasms - pathology Male Middle Aged Multivariate Analysis NADPH Oxidase 4 - metabolism Progression-Free Survival |
| title | Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma |
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