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Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer

At present, the overall genetic and epigenetic effects of Krüppel‐like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivar...

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Autores principales: Meng, Jialin, Lu, Xiaofan, Zhou, Yujie, Zhang, Meng, Gao, Lei, Gao, Shenglin, Yan, Fangrong, Liang, Chaozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214179/
https://www.ncbi.nlm.nih.gov/pubmed/32281273
http://dx.doi.org/10.1111/jcmm.15242
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author Meng, Jialin
Lu, Xiaofan
Zhou, Yujie
Zhang, Meng
Gao, Lei
Gao, Shenglin
Yan, Fangrong
Liang, Chaozhao
author_facet Meng, Jialin
Lu, Xiaofan
Zhou, Yujie
Zhang, Meng
Gao, Lei
Gao, Shenglin
Yan, Fangrong
Liang, Chaozhao
author_sort Meng, Jialin
collection PubMed
description At present, the overall genetic and epigenetic effects of Krüppel‐like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P < .001) and validated in the MSKCC (P < .001) and GSE116918 cohorts (P = .006). Demethylation of KLF5 by 5‐azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF‐F were more likely to respond to immunotherapy (P < .001) and bicalutamide (P < .001). In summary, we found that the KLFs and clinical feature‐based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management.
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spelling pubmed-72141792020-05-13 Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer Meng, Jialin Lu, Xiaofan Zhou, Yujie Zhang, Meng Gao, Lei Gao, Shenglin Yan, Fangrong Liang, Chaozhao J Cell Mol Med Original Articles At present, the overall genetic and epigenetic effects of Krüppel‐like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P < .001) and validated in the MSKCC (P < .001) and GSE116918 cohorts (P = .006). Demethylation of KLF5 by 5‐azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF‐F were more likely to respond to immunotherapy (P < .001) and bicalutamide (P < .001). In summary, we found that the KLFs and clinical feature‐based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management. John Wiley and Sons Inc. 2020-04-13 2020-05 /pmc/articles/PMC7214179/ /pubmed/32281273 http://dx.doi.org/10.1111/jcmm.15242 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Meng, Jialin
Lu, Xiaofan
Zhou, Yujie
Zhang, Meng
Gao, Lei
Gao, Shenglin
Yan, Fangrong
Liang, Chaozhao
Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title_full Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title_fullStr Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title_full_unstemmed Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title_short Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
title_sort characterization of the prognostic values and response to immunotherapy/chemotherapy of krüppel‐like factors in prostate cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214179/
https://www.ncbi.nlm.nih.gov/pubmed/32281273
http://dx.doi.org/10.1111/jcmm.15242
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