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Age-correlated protein and transcript expression in breast cancer and normal breast tissues is dominated by host endocrine effects Osako, Tomo; Lee, Hakwoo; Turashvili, Gulisa; Chiu, Derek; McKinney, Steven; Joosten, Stacey; Wilkinson, Darcy; Nielsen, Torsten; Zwart, Wilbert; Emerman, Joanne T.; Eaves, Connie; Caldas, Carlos; Aparicio, Samuel, 1963-
Abstract
The magnitude and scope of intrinsic age-correlated and host endocrine age-correlated gene expression in breast cancer is not well understood. From age-correlated gene expression in 3071 breast cancer transcriptomes and epithelial protein expression of 42 markers in 5001 breast cancers and 537 normal breast tissues, we identified a majority of age-correlated genes as putatively regulated by age-dependent estrogen signaling. Surprisingly these include the chromatin modifier EZH2 with negative age correlation and associated H3K27me3, with an inverse positive age correlation. Among TCGA-lung, thyroid, kidney and prostate transcriptomes, the largest overlap with breast cancer in age-correlated transcripts was in lung cancer, where about 1/3 of overlapping age-correlated transcripts appeared estrogen regulated. Age-quartile stratified outcomes analysis of 3,500 breast cancers using EZH2, H3K27me3, FOXA1 and BCL2 proteins revealed distinct age-related prognostic significance. Age correlation in gene expression may thus be an important factor in ER, EZH2, H3K27me3 and other biomarker assessment and treatment strategies.
Item Metadata
Title |
Age-correlated protein and transcript expression in breast cancer and normal breast tissues is dominated by host endocrine effects
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Creator | |
Contributor | |
Publisher |
Nature Cancer
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Date Issued |
2020-03-20
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Description |
The magnitude and scope of intrinsic age-correlated and host endocrine age-correlated gene
expression in breast cancer is not well understood. From age-correlated gene expression in 3071
breast cancer transcriptomes and epithelial protein expression of 42 markers in 5001 breast cancers and 537 normal breast tissues, we identified a majority of age-correlated genes as putatively
regulated by age-dependent estrogen signaling. Surprisingly these include the chromatin modifier EZH2 with negative age correlation and associated H3K27me3, with an inverse positive age
correlation. Among TCGA-lung, thyroid, kidney and prostate transcriptomes, the largest overlap
with breast cancer in age-correlated transcripts was in lung cancer, where about 1/3 of overlapping
age-correlated transcripts appeared estrogen regulated. Age-quartile stratified outcomes analysis
of 3,500 breast cancers using EZH2, H3K27me3, FOXA1 and BCL2 proteins revealed distinct
age-related prognostic significance. Age correlation in gene expression may thus be an important
factor in ER, EZH2, H3K27me3 and other biomarker assessment and treatment strategies.
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Genre | |
Type | |
Language |
eng
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Date Available |
2021-06-29
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0398731
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URI | |
Affiliation | |
Citation |
Osako, T., Lee, H., Turashvili, G. et al. Age-correlated protein and transcript expression in breast cancer and normal breast tissues is dominated by host endocrine effects. Nat Cancer 1, 518–532 (2020)
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Publisher DOI |
10.1038/s43018-020-0060-4
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty; Researcher; Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International