Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers

Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Yang Wang [verfasserIn] Kexin Yi [verfasserIn] Baoyue Chen [verfasserIn] Bailin Zhang [verfasserIn] Gao Jidong [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer

Übergeordnetes Werk:	In: Frontiers in Molecular Biosciences - Frontiers Media S.A., 2015, 10(2024)
Übergeordnetes Werk:	volume:10 ; year:2024

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmolb.2023.1340917

Katalog-ID:	DOAJ097509442

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520			\|a Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.
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allfields	10.3389/fmolb.2023.1340917 doi (DE-627)DOAJ097509442 (DE-599)DOAJ3ad13e70d2f74f2b8745fad863998f7b DE-627 ger DE-627 rakwb eng QH301-705.5 Yang Wang verfasserin aut Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer Biology (General) Kexin Yi verfasserin aut Baoyue Chen verfasserin aut Bailin Zhang verfasserin aut Gao Jidong verfasserin aut Gao Jidong verfasserin aut In Frontiers in Molecular Biosciences Frontiers Media S.A., 2015 10(2024) (DE-627)820039691 (DE-600)2814330-9 2296889X nnns volume:10 year:2024 https://doi.org/10.3389/fmolb.2023.1340917 kostenfrei https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b kostenfrei https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full kostenfrei https://doaj.org/toc/2296-889X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 10 2024
spelling	10.3389/fmolb.2023.1340917 doi (DE-627)DOAJ097509442 (DE-599)DOAJ3ad13e70d2f74f2b8745fad863998f7b DE-627 ger DE-627 rakwb eng QH301-705.5 Yang Wang verfasserin aut Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer Biology (General) Kexin Yi verfasserin aut Baoyue Chen verfasserin aut Bailin Zhang verfasserin aut Gao Jidong verfasserin aut Gao Jidong verfasserin aut In Frontiers in Molecular Biosciences Frontiers Media S.A., 2015 10(2024) (DE-627)820039691 (DE-600)2814330-9 2296889X nnns volume:10 year:2024 https://doi.org/10.3389/fmolb.2023.1340917 kostenfrei https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b kostenfrei https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full kostenfrei https://doaj.org/toc/2296-889X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 10 2024
allfields_unstemmed	10.3389/fmolb.2023.1340917 doi (DE-627)DOAJ097509442 (DE-599)DOAJ3ad13e70d2f74f2b8745fad863998f7b DE-627 ger DE-627 rakwb eng QH301-705.5 Yang Wang verfasserin aut Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer Biology (General) Kexin Yi verfasserin aut Baoyue Chen verfasserin aut Bailin Zhang verfasserin aut Gao Jidong verfasserin aut Gao Jidong verfasserin aut In Frontiers in Molecular Biosciences Frontiers Media S.A., 2015 10(2024) (DE-627)820039691 (DE-600)2814330-9 2296889X nnns volume:10 year:2024 https://doi.org/10.3389/fmolb.2023.1340917 kostenfrei https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b kostenfrei https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full kostenfrei https://doaj.org/toc/2296-889X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 10 2024
allfieldsGer	10.3389/fmolb.2023.1340917 doi (DE-627)DOAJ097509442 (DE-599)DOAJ3ad13e70d2f74f2b8745fad863998f7b DE-627 ger DE-627 rakwb eng QH301-705.5 Yang Wang verfasserin aut Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer Biology (General) Kexin Yi verfasserin aut Baoyue Chen verfasserin aut Bailin Zhang verfasserin aut Gao Jidong verfasserin aut Gao Jidong verfasserin aut In Frontiers in Molecular Biosciences Frontiers Media S.A., 2015 10(2024) (DE-627)820039691 (DE-600)2814330-9 2296889X nnns volume:10 year:2024 https://doi.org/10.3389/fmolb.2023.1340917 kostenfrei https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b kostenfrei https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full kostenfrei https://doaj.org/toc/2296-889X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 10 2024
allfieldsSound	10.3389/fmolb.2023.1340917 doi (DE-627)DOAJ097509442 (DE-599)DOAJ3ad13e70d2f74f2b8745fad863998f7b DE-627 ger DE-627 rakwb eng QH301-705.5 Yang Wang verfasserin aut Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets. proteome-wide association study transcriptome-wide association study plasma proteins mendelian randomization breast cancer Biology (General) Kexin Yi verfasserin aut Baoyue Chen verfasserin aut Bailin Zhang verfasserin aut Gao Jidong verfasserin aut Gao Jidong verfasserin aut In Frontiers in Molecular Biosciences Frontiers Media S.A., 2015 10(2024) (DE-627)820039691 (DE-600)2814330-9 2296889X nnns volume:10 year:2024 https://doi.org/10.3389/fmolb.2023.1340917 kostenfrei https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b kostenfrei https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full kostenfrei https://doaj.org/toc/2296-889X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 10 2024
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title	Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers
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title_full	Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers
author_sort	Yang Wang
journal	Frontiers in Molecular Biosciences
journalStr	Frontiers in Molecular Biosciences
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author_browse	Yang Wang Kexin Yi Baoyue Chen Bailin Zhang Gao Jidong
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doi_str_mv	10.3389/fmolb.2023.1340917
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title_sort	elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers
callnumber	QH301-705.5
title_auth	Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers
abstract	Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.
abstractGer	Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.
abstract_unstemmed	Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.
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title_short	Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers
url	https://doi.org/10.3389/fmolb.2023.1340917 https://doaj.org/article/3ad13e70d2f74f2b8745fad863998f7b https://www.frontiersin.org/articles/10.3389/fmolb.2023.1340917/full https://doaj.org/toc/2296-889X
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author2	Kexin Yi Baoyue Chen Bailin Zhang Gao Jidong
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up_date	2024-07-04T01:31:51.692Z
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