Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer
Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and id...
Ausführliche Beschreibung
Autor*in: |
Hao Chen [verfasserIn] Wei Chong [verfasserIn] Xiaorong Yang [verfasserIn] Yuan Zhang [verfasserIn] Shaowei Sang [verfasserIn] Xiangchun Li [verfasserIn] Ming Lu [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
In: OncoImmunology - Taylor & Francis Group, 2020, 9(2020), 1 |
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Übergeordnetes Werk: |
volume:9 ; year:2020 ; number:1 |
Links: |
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DOI / URN: |
10.1080/2162402X.2020.1788252 |
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Katalog-ID: |
DOAJ070710694 |
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10.1080/2162402X.2020.1788252 doi (DE-627)DOAJ070710694 (DE-599)DOAJ9c30bcc33c134bfd8f286e4b9ccc2883 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Hao Chen verfasserin aut Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. mutational signature tnbc immune infiltration tumor mutation burden Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Wei Chong verfasserin aut Xiaorong Yang verfasserin aut Yuan Zhang verfasserin aut Shaowei Sang verfasserin aut Xiangchun Li verfasserin aut Ming Lu verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 9(2020), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:9 year:2020 number:1 https://doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/article/9c30bcc33c134bfd8f286e4b9ccc2883 kostenfrei http://dx.doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 1 |
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10.1080/2162402X.2020.1788252 doi (DE-627)DOAJ070710694 (DE-599)DOAJ9c30bcc33c134bfd8f286e4b9ccc2883 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Hao Chen verfasserin aut Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. mutational signature tnbc immune infiltration tumor mutation burden Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Wei Chong verfasserin aut Xiaorong Yang verfasserin aut Yuan Zhang verfasserin aut Shaowei Sang verfasserin aut Xiangchun Li verfasserin aut Ming Lu verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 9(2020), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:9 year:2020 number:1 https://doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/article/9c30bcc33c134bfd8f286e4b9ccc2883 kostenfrei http://dx.doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 1 |
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10.1080/2162402X.2020.1788252 doi (DE-627)DOAJ070710694 (DE-599)DOAJ9c30bcc33c134bfd8f286e4b9ccc2883 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Hao Chen verfasserin aut Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. mutational signature tnbc immune infiltration tumor mutation burden Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Wei Chong verfasserin aut Xiaorong Yang verfasserin aut Yuan Zhang verfasserin aut Shaowei Sang verfasserin aut Xiangchun Li verfasserin aut Ming Lu verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 9(2020), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:9 year:2020 number:1 https://doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/article/9c30bcc33c134bfd8f286e4b9ccc2883 kostenfrei http://dx.doi.org/10.1080/2162402X.2020.1788252 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 1 |
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RC581-607 RC254-282 Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer mutational signature tnbc immune infiltration tumor mutation burden |
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Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer |
abstract |
Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. |
abstractGer |
Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. |
abstract_unstemmed |
Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C < T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping. |
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