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 3,071 breast cancer transcriptomes and epithelial protein expression of 42 markers in 5,001 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 included genes encoding the chromatin modifier EZH2 (which had a negative age correlation) and associated H3K27me3 (which had an inverse, positive age correlation). Among The Cancer Genome Atlas lung, thyroid, kidney and prostate transcriptomes, the largest overlap with breast cancer in age-correlated transcripts was lung cancer, for which about one-third of overlapping age-correlated transcripts appeared to be 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.

乳腺癌中内在年龄相关和宿主内分泌年龄相关基因表达的幅度和范围尚不清楚。从 3,071 个乳腺癌转录组中与年龄相关的基因表达和 5,001 个乳腺癌和 537 个正常乳腺组织中 42 个标志物的上皮蛋白表达，我们确定了大多数与年龄相关的基因假定受年龄依赖性雌激素信号传导的调节。令人惊讶的是，这些包括编码染色质修饰因子 EZH2（具有负年龄相关性）和相关 H3K27me3（具有反向正年龄相关性）的基因。在癌症基因组图谱肺、甲状腺、肾脏和前列腺转录组中，与年龄相关的转录组中与乳腺癌最大的重叠是肺癌，其中约三分之一与年龄相关的重叠转录本似乎受到雌激素的调节。使用 EZH2、H3K27me3、FOXA1 和 BCL2 蛋白对 3,500 例乳腺癌进行年龄四分位分层结果分析揭示了与年龄相关的不同预后意义。因此，基因表达的年龄相关性可能是 ER、EZH2、H3K27me3 和其他生物标志物评估和治疗策略的重要因素。