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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.