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BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in...
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Published in: | International journal of molecular sciences 2022-03, Vol.23 (7), p.3754 |
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description | BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted. |
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They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23073754</identifier><identifier>PMID: 35409110</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Bioinformatics ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; BRCA1 protein ; BRCA1 Protein - genetics ; BRCA1 Protein - metabolism ; BRCA1/2 ; BRCA2 protein ; BRCA2 Protein - genetics ; Breast - pathology ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Catalytic activity ; Cell cycle ; Copy number ; Deoxyribonucleic acid ; DNA ; DNA repair ; Estrogen receptors ; Estrogens ; Female ; Gene expression ; Genes ; Genes, BRCA2 ; Humans ; Lymph nodes ; multiomics ; Mutation ; Progesterone ; Progesterone receptors ; Prognosis ; prognostic biomarkers ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Therapeutic applications ; Therapeutic targets ; Transcription ; Womens health</subject><ispartof>International journal of molecular sciences, 2022-03, Vol.23 (7), p.3754</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-f36d201c6df9434604e487cdebf3e8e24336e3d0c1cae851c7d698e0d8f761273</citedby><cites>FETCH-LOGICAL-c478t-f36d201c6df9434604e487cdebf3e8e24336e3d0c1cae851c7d698e0d8f761273</cites><orcidid>0000-0002-6285-3901 ; 0000-0002-0774-7911</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2649054976/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2649054976?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35409110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Tong Yi</creatorcontrib><creatorcontrib>Park, Kyoung Sik</creatorcontrib><creatorcontrib>Nam, Sang Eun</creatorcontrib><creatorcontrib>Yoo, Young Bum</creatorcontrib><creatorcontrib>Park, Won Seo</creatorcontrib><creatorcontrib>Yun, Ik Jin</creatorcontrib><title>BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.</description><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>BRCA1 protein</subject><subject>BRCA1 Protein - genetics</subject><subject>BRCA1 Protein - metabolism</subject><subject>BRCA1/2</subject><subject>BRCA2 protein</subject><subject>BRCA2 Protein - genetics</subject><subject>Breast - pathology</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Catalytic activity</subject><subject>Cell cycle</subject><subject>Copy number</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA repair</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genes, BRCA2</subject><subject>Humans</subject><subject>Lymph nodes</subject><subject>multiomics</subject><subject>Mutation</subject><subject>Progesterone</subject><subject>Progesterone receptors</subject><subject>Prognosis</subject><subject>prognostic biomarkers</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Therapeutic applications</subject><subject>Therapeutic targets</subject><subject>Transcription</subject><subject>Womens health</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkc1LHDEYh0NpqVZ767kM9NKDW_P9cRHcVVtBqGh7Du9m3myzzk5sMiv0v--sa2UthCQkDw-_5EfIB0a_COHocVquKhfUCKPkK7LPJOcTSrV5vbPfI-9qXVLKBVfuLdkTSlLHGN0nZ9Ob2Sk75s0tlgesDYyjmaa8gnKHpYm5NNd5M5W86HNNtUl9My0IdWhmUELqR_SQvInQVXz_tB6QnxfnP2bfJlffv17OTq8mQRo7TKLQLacs6DY6KaSmEqU1ocV5FGiRSyE0ipYGFgCtYsG02lmkrY1GM27EAbncetsMS39f0pjyj8-Q_ONBLgsPZUihQz8H0NwFJh1GCWDmklGnQARugEelR9fJ1nW_nq-wDdgPBboX0pc3ffrlF_nBW-esMZswn58EJf9eYx38KtWAXQc95nX1XEunrDNMjein_9BlXpd-_KpHiirpzCbR0ZYKJddaMD6HYdRvqva7VY_4x90HPMP_uhV_AR-Nork</recordid><startdate>20220329</startdate><enddate>20220329</enddate><creator>Jin, Tong Yi</creator><creator>Park, Kyoung Sik</creator><creator>Nam, Sang Eun</creator><creator>Yoo, Young Bum</creator><creator>Park, Won Seo</creator><creator>Yun, Ik Jin</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6285-3901</orcidid><orcidid>https://orcid.org/0000-0002-0774-7911</orcidid></search><sort><creationdate>20220329</creationdate><title>BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma</title><author>Jin, Tong Yi ; Park, Kyoung Sik ; Nam, Sang Eun ; Yoo, Young Bum ; Park, Won Seo ; Yun, Ik Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-f36d201c6df9434604e487cdebf3e8e24336e3d0c1cae851c7d698e0d8f761273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>BRCA1 protein</topic><topic>BRCA1 Protein - genetics</topic><topic>BRCA1 Protein - metabolism</topic><topic>BRCA1/2</topic><topic>BRCA2 protein</topic><topic>BRCA2 Protein - genetics</topic><topic>Breast - pathology</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Catalytic activity</topic><topic>Cell cycle</topic><topic>Copy number</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA repair</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genes, BRCA2</topic><topic>Humans</topic><topic>Lymph nodes</topic><topic>multiomics</topic><topic>Mutation</topic><topic>Progesterone</topic><topic>Progesterone receptors</topic><topic>Prognosis</topic><topic>prognostic biomarkers</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Therapeutic applications</topic><topic>Therapeutic targets</topic><topic>Transcription</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Tong Yi</creatorcontrib><creatorcontrib>Park, Kyoung Sik</creatorcontrib><creatorcontrib>Nam, Sang Eun</creatorcontrib><creatorcontrib>Yoo, Young Bum</creatorcontrib><creatorcontrib>Park, Won Seo</creatorcontrib><creatorcontrib>Yun, Ik Jin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Databases</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Tong Yi</au><au>Park, Kyoung Sik</au><au>Nam, Sang Eun</au><au>Yoo, Young Bum</au><au>Park, Won Seo</au><au>Yun, Ik Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2022-03-29</date><risdate>2022</risdate><volume>23</volume><issue>7</issue><spage>3754</spage><pages>3754-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35409110</pmid><doi>10.3390/ijms23073754</doi><orcidid>https://orcid.org/0000-0002-6285-3901</orcidid><orcidid>https://orcid.org/0000-0002-0774-7911</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Bioinformatics Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism BRCA1 protein BRCA1 Protein - genetics BRCA1 Protein - metabolism BRCA1/2 BRCA2 protein BRCA2 Protein - genetics Breast - pathology Breast cancer Breast carcinoma Breast Neoplasms - diagnosis Breast Neoplasms - genetics Breast Neoplasms - pathology Catalytic activity Cell cycle Copy number Deoxyribonucleic acid DNA DNA repair Estrogen receptors Estrogens Female Gene expression Genes Genes, BRCA2 Humans Lymph nodes multiomics Mutation Progesterone Progesterone receptors Prognosis prognostic biomarkers RNA, Messenger - genetics RNA, Messenger - metabolism Therapeutic applications Therapeutic targets Transcription Womens health |
title | BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma |
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