Bauer Brent A, Schmidt Caleb M, Ruddy Kathryn J, Olson Janet E, Meydan Cem, Schmidt Julian C, Smith Sheena Y, Couch Fergus J, Earls John C, Price Nathan D, Dudley Joel T, Mason Christopher E, Zhang Bodi, Phipps Stephen M, Schmidt Michael A
Mayo Clinic, Rochester, MN 55905, USA.
Sovaris Aerospace, Boulder, CO 80302, USA.
Metabolites. 2024 Jul 20;14(7):396. doi: 10.3390/metabo14070396.
Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.
乳腺癌在全球造成了巨大负担。虽然生存率在稳步提高,但仍有许多有待阐明的问题。这项观察性、单时间点、多组学研究在一组乳腺癌幸存者(BCS)和年龄匹配的健康对照人群(N = 100)中运用了基因组学、蛋白质组学、靶向和非靶向代谢组学以及宏基因组学,提供了乳腺癌幸存者的深度分子表型分析。在本研究中,BCS队列的乳腺癌多基因风险评分显著高于对照组。肉碱和己酰肉碱存在显著差异。几种胆汁酸和脂肪酸代谢物也有显著不同,最明显的是欧米伽-3指数(O3I)(在BCS中显著更低)。蛋白质组学和宏基因组学分析确定了组间和通路差异,值得进一步研究。本研究建立的数据库为乳腺癌幸存者这一数据匮乏领域贡献了大量数据,具备识别模式和新见解的能力,从而能推动新假设的提出并为未来研究提供信息。在未接受过治疗、新诊断的患者中扩大该数据库,控制治疗混杂因素,并贯穿疾病进展过程,可用于描绘和背景化乳腺癌及乳腺癌幸存者情况,有可能催生对抗该疾病的新策略并改善患者生活质量。