Specific cancer types and prognosis in patients with variations in the KEAP1‐NRF2 system: A retrospective cohort study
The KEAP1–NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C‐CAT database, which contains t...
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| Veröffentlicht in: | Cancer science 2024-12, Vol.115 (12), p.4034-4044 |
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| creator | Iwasaki, Tomoyuki Shirota, Hidekazu Sasaki, Keiju Ouchi, Kota Nakayama, Yuki Oshikiri, Hiroyuki Otsuki, Akihito Suzuki, Takafumi Yamamoto, Masayuki Ishioka, Chikashi |
| description | The KEAP1–NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C‐CAT database, which contains the gene‐panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1–NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.
This study examined variants in the KEAP1–NRF2 system for their correlation with cancer type specificity, prognosis, and biological characteristics from the pan‐cancer cohort. The results showed that the presence of variants in NRF2‐DLG, NRF2‐ETGE motifs, and KEAP1 gene play an important role in predicting patient prognosis and defining new therapeutic targets. |
| doi_str_mv | 10.1111/cas.16355 |
| format | Article |
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This study examined variants in the KEAP1–NRF2 system for their correlation with cancer type specificity, prognosis, and biological characteristics from the pan‐cancer cohort. The results showed that the presence of variants in NRF2‐DLG, NRF2‐ETGE motifs, and KEAP1 gene play an important role in predicting patient prognosis and defining new therapeutic targets.</description><identifier>ISSN: 1347-9032</identifier><identifier>ISSN: 1349-7006</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.16355</identifier><identifier>PMID: 39327066</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Algorithms ; Amino acids ; Analysis ; Cancer patients ; Cancer therapies ; Carcinogenesis ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; CGP test ; Chemotherapy ; C‐CAT data ; Development and progression ; Esophageal cancer ; Esophageal carcinoma ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene mutations ; Genes ; Genetic aspects ; Genetic diversity ; Genomes ; Genomics ; Humans ; KEAP1 ; Kelch-Like ECH-Associated Protein 1 - genetics ; Kelch-Like ECH-Associated Protein 1 - metabolism ; Lung cancer ; Lung carcinoma ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Male ; Malignancy ; Medical prognosis ; Mutation ; National health insurance ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; NRF2 ; NRF2 protein ; Original ; ORIGINAL ARTICLE ; Oxidative stress ; Patients ; Prognosis ; Retrospective Studies ; Software ; solid tumor ; Solid tumors ; Squamous cell carcinoma ; Tumors</subject><ispartof>Cancer science, 2024-12, Vol.115 (12), p.4034-4044</ispartof><rights>2024 The Author(s). published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>COPYRIGHT 2024 John Wiley & Sons, Inc.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4015-5cc72983493a6286308e1e0cf08c7b4a0a9a706236168d7a155a144489ad54833</cites><orcidid>0000-0002-3023-1227 ; 0000-0001-9154-9004 ; 0000-0002-5572-1337</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611756/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611756/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1416,11561,27923,27924,45573,45574,46051,46475,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39327066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwasaki, Tomoyuki</creatorcontrib><creatorcontrib>Shirota, Hidekazu</creatorcontrib><creatorcontrib>Sasaki, Keiju</creatorcontrib><creatorcontrib>Ouchi, Kota</creatorcontrib><creatorcontrib>Nakayama, Yuki</creatorcontrib><creatorcontrib>Oshikiri, Hiroyuki</creatorcontrib><creatorcontrib>Otsuki, Akihito</creatorcontrib><creatorcontrib>Suzuki, Takafumi</creatorcontrib><creatorcontrib>Yamamoto, Masayuki</creatorcontrib><creatorcontrib>Ishioka, Chikashi</creatorcontrib><title>Specific cancer types and prognosis in patients with variations in the KEAP1‐NRF2 system: A retrospective cohort study</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>The KEAP1–NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C‐CAT database, which contains the gene‐panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1–NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.
This study examined variants in the KEAP1–NRF2 system for their correlation with cancer type specificity, prognosis, and biological characteristics from the pan‐cancer cohort. The results showed that the presence of variants in NRF2‐DLG, NRF2‐ETGE motifs, and KEAP1 gene play an important role in predicting patient prognosis and defining new therapeutic targets.</description><subject>Algorithms</subject><subject>Amino acids</subject><subject>Analysis</subject><subject>Cancer patients</subject><subject>Cancer therapies</subject><subject>Carcinogenesis</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>CGP test</subject><subject>Chemotherapy</subject><subject>C‐CAT data</subject><subject>Development and progression</subject><subject>Esophageal cancer</subject><subject>Esophageal carcinoma</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>KEAP1</subject><subject>Kelch-Like ECH-Associated Protein 1 - genetics</subject><subject>Kelch-Like ECH-Associated Protein 1 - metabolism</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Mutation</subject><subject>National health insurance</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NRF2</subject><subject>NRF2 protein</subject><subject>Original</subject><subject>ORIGINAL ARTICLE</subject><subject>Oxidative stress</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Software</subject><subject>solid tumor</subject><subject>Solid tumors</subject><subject>Squamous cell carcinoma</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ksFu1DAQhiMEoqVw4AWQJS5wyNaOHcfhgqJVC4gKEIWz5TrOrqvEDrazJbc-Qp-RJ2G6WwpFYB9sjb_5x_9osuwpwQsC61CruCCcluW9bJ9QVucVxvz-9l7lNabFXvYoxnOMKWc1e5jt0ZoWFeZ8P_t-OhptO6uRVk6bgNI8moiUa9EY_Mr5aCOyDo0qWeNSRBc2rdFGBQsB77ZvaW3Q-6PmE_lxefXh83GB4hyTGV6hBgWTgo9QItmNQdqvfUgopqmdH2cPOtVH8-TmPMi-Hh99Wb7NTz6-ebdsTnLNMCnzUuuqqAWYoooXglMsDDFYd1jo6owprGoFTgrKCRdtpUhZKsIYE7VqSyYoPche73TH6WwwrQYTQfVyDHZQYZZeWXn3xdm1XPmNJIQTUpUcFF7cKAT_bTIxycFGbfpeOeOnKCkhGP5a1RWgz_9Cz_0UHPgDCjwIRgX-Ta1Ub6R1nYfC-lpUNoKICjNKC6AW_6Bgt2aw2jvTWYjfSXi5S9DQ8hhMd2uSYHk9JxLmRG7nBNhnf3bllvw1GAAc7oALqDL_X0kum9Od5E-aucYD</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Iwasaki, Tomoyuki</creator><creator>Shirota, Hidekazu</creator><creator>Sasaki, Keiju</creator><creator>Ouchi, Kota</creator><creator>Nakayama, Yuki</creator><creator>Oshikiri, Hiroyuki</creator><creator>Otsuki, Akihito</creator><creator>Suzuki, Takafumi</creator><creator>Yamamoto, Masayuki</creator><creator>Ishioka, Chikashi</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3023-1227</orcidid><orcidid>https://orcid.org/0000-0001-9154-9004</orcidid><orcidid>https://orcid.org/0000-0002-5572-1337</orcidid></search><sort><creationdate>202412</creationdate><title>Specific cancer types and prognosis in patients with variations in the KEAP1‐NRF2 system: A retrospective cohort study</title><author>Iwasaki, Tomoyuki ; Shirota, Hidekazu ; Sasaki, Keiju ; Ouchi, Kota ; Nakayama, Yuki ; Oshikiri, Hiroyuki ; Otsuki, Akihito ; Suzuki, Takafumi ; Yamamoto, Masayuki ; Ishioka, Chikashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4015-5cc72983493a6286308e1e0cf08c7b4a0a9a706236168d7a155a144489ad54833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Algorithms</topic><topic>Amino acids</topic><topic>Analysis</topic><topic>Cancer patients</topic><topic>Cancer therapies</topic><topic>Carcinogenesis</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>CGP test</topic><topic>Chemotherapy</topic><topic>C‐CAT data</topic><topic>Development and progression</topic><topic>Esophageal cancer</topic><topic>Esophageal carcinoma</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>KEAP1</topic><topic>Kelch-Like ECH-Associated Protein 1 - genetics</topic><topic>Kelch-Like ECH-Associated Protein 1 - metabolism</topic><topic>Lung cancer</topic><topic>Lung carcinoma</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Mutation</topic><topic>National health insurance</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NRF2</topic><topic>NRF2 protein</topic><topic>Original</topic><topic>ORIGINAL ARTICLE</topic><topic>Oxidative stress</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Software</topic><topic>solid tumor</topic><topic>Solid tumors</topic><topic>Squamous cell carcinoma</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwasaki, Tomoyuki</creatorcontrib><creatorcontrib>Shirota, Hidekazu</creatorcontrib><creatorcontrib>Sasaki, Keiju</creatorcontrib><creatorcontrib>Ouchi, Kota</creatorcontrib><creatorcontrib>Nakayama, Yuki</creatorcontrib><creatorcontrib>Oshikiri, Hiroyuki</creatorcontrib><creatorcontrib>Otsuki, Akihito</creatorcontrib><creatorcontrib>Suzuki, Takafumi</creatorcontrib><creatorcontrib>Yamamoto, Masayuki</creatorcontrib><creatorcontrib>Ishioka, Chikashi</creatorcontrib><collection>Wiley-Blackwell Open Access Collection</collection><collection>Wiley Online Library Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwasaki, Tomoyuki</au><au>Shirota, Hidekazu</au><au>Sasaki, Keiju</au><au>Ouchi, Kota</au><au>Nakayama, Yuki</au><au>Oshikiri, Hiroyuki</au><au>Otsuki, Akihito</au><au>Suzuki, Takafumi</au><au>Yamamoto, Masayuki</au><au>Ishioka, Chikashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Specific cancer types and prognosis in patients with variations in the KEAP1‐NRF2 system: A retrospective cohort study</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2024-12</date><risdate>2024</risdate><volume>115</volume><issue>12</issue><spage>4034</spage><epage>4044</epage><pages>4034-4044</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract>The KEAP1–NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C‐CAT database, which contains the gene‐panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1–NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.
This study examined variants in the KEAP1–NRF2 system for their correlation with cancer type specificity, prognosis, and biological characteristics from the pan‐cancer cohort. The results showed that the presence of variants in NRF2‐DLG, NRF2‐ETGE motifs, and KEAP1 gene play an important role in predicting patient prognosis and defining new therapeutic targets.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>39327066</pmid><doi>10.1111/cas.16355</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3023-1227</orcidid><orcidid>https://orcid.org/0000-0001-9154-9004</orcidid><orcidid>https://orcid.org/0000-0002-5572-1337</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2024-12, Vol.115 (12), p.4034-4044 |
| issn | 1347-9032 1349-7006 1349-7006 |
| language | eng |
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| source | Wiley-Blackwell Open Access Collection; MEDLINE; Wiley Online Library Journals; DOAJ Directory of Open Access Journals; PubMed Central |
| subjects | Algorithms Amino acids Analysis Cancer patients Cancer therapies Carcinogenesis Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology CGP test Chemotherapy C‐CAT data Development and progression Esophageal cancer Esophageal carcinoma Female Gene expression Gene Expression Regulation, Neoplastic Gene mutations Genes Genetic aspects Genetic diversity Genomes Genomics Humans KEAP1 Kelch-Like ECH-Associated Protein 1 - genetics Kelch-Like ECH-Associated Protein 1 - metabolism Lung cancer Lung carcinoma Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - mortality Lung Neoplasms - pathology Male Malignancy Medical prognosis Mutation National health insurance Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism NRF2 NRF2 protein Original ORIGINAL ARTICLE Oxidative stress Patients Prognosis Retrospective Studies Software solid tumor Solid tumors Squamous cell carcinoma Tumors |
| title | Specific cancer types and prognosis in patients with variations in the KEAP1‐NRF2 system: A retrospective cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T16%3A56%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Specific%20cancer%20types%20and%20prognosis%20in%20patients%20with%20variations%20in%20the%20KEAP1%E2%80%90NRF2%20system:%20A%20retrospective%20cohort%20study&rft.jtitle=Cancer%20science&rft.au=Iwasaki,%20Tomoyuki&rft.date=2024-12&rft.volume=115&rft.issue=12&rft.spage=4034&rft.epage=4044&rft.pages=4034-4044&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.16355&rft_dat=%3Cgale_pubme%3EA818704332%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3134984380&rft_id=info:pmid/39327066&rft_galeid=A818704332&rfr_iscdi=true |