PO.CL04.02 · 临床研究
黑人与白人乳腺癌幸存者的系统性分子差异：超越社会经济决定因素
Systemic molecular disparities in Black vs. White breast cancer survivors: Beyond socioeconomic determinants
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的：非西班牙裔黑人(NHB)女性的乳腺癌(BC)死亡率比非西班牙裔白人(NHW)女性高27%。本研究的目的是探究NHB乳腺癌幸存者更高死亡率背后的分子机制，且独立于生活方式和社会经济因素。
实验：从NHW和NHB乳腺癌幸存者(各n=12，治疗后6个月至3年)以及无癌参与者(各n=6)中采集白膜层。对临床变量进行主成分分析(PCA)和Fisher精确检验。基因表达采用nCounter免疫学面板(594个基因)、代谢通路面板(768个基因)以及Qiagen RT²Profiler PCR阵列人类DNA修复试剂盒(84个基因)进行测量。对两组比较进行差异表达分析：(A)黑人与白人乳腺癌幸存者，(B)黑人与白人非癌症对照。采用双样本Student t检验并进行多重检验校正(Benjamini-Hochberg错误发现率(FDR))，使用log2 FC并按显著性筛选(p<0.05，FDR<0.25，|倍数变化|>2)。进行了Ingenuity通路分析(IPA)，将-log p值≥1.3且Z评分≥2或≤-2的通路视为显著。
结果：临床因素(年龄、BMI和治疗)的PCA和分期分布(Fisher精确检验)显示NHB和NHW乳腺癌幸存者之间具有相似的特征，提示下游分析中的分子差异不太可能由临床或生活方式因素驱动。差异表达分析提示，非癌症NHB和NHW对照之间仅有两个基因存在显著差异，但癌症幸存者之间有92个基因(包括IL8和POLB)存在显著改变。这些发现提示差异表达模式是由癌症幸存状态而非基线种族差异所驱动。随后用IPA分析这92个基因，17条通路被判定为显著。Th1以及TP53表达和降解通路更为活跃。在NHB幸存者中发现无碱基位点修复通路受到抑制，这与我们之前的报告一致。
结论：我们的初步研究表明，尽管临床特征相似，NHB和NHW乳腺癌幸存者表现出不同的分子特征。未来，我们计划验证这些通路，并利用TCGA等公共数据库评估这些基因如何影响癌症生存。解决这些通路差异可能是实现乳腺癌幸存者真正公平的关键。
查看英文原文 English abstract
Objective: Mortality from breast cancer (BC) is 27% higher among non-Hispanic Black (NHB) than among non-Hispanic White (NHW) women. The objective of this study is to investigate molecular mechanisms underlying the higher mortality rate in NHB BC survivors, independent of lifestyle and socioeconomic factors.
Experiment: Buffy coats were collected from NHW and NHB BC survivors (n=12 each, 6 months - 3 years post-treatment) and from cancer-free participants (n=6 each). Principal Component Analysis (PCA) and Fisher's exact tests were performed on clinical variables. Gene expression was measured with the nCounter Immunology Panel (594 genes), Metabolic Pathways Panel (768 genes), and Qiagen RT² Profiler PCR Array Human DNA Repair Kit (84 genes). Differential expression analysis was performed for two comparisons: (A) Black vs. White BC survivors, and (B) Black vs. White non-cancer controls. A two-sample Student's t-test with multiple testing correction (Benjamini-Hochberg false discovery rate (FDR)) was performed with log 2 FC and filtered for significance (p < 0.05, FDR < 0.25, |fold change| > 2). An Ingenuity Pathway Analysis (IPA) was performed, and pathways with -log p value>=1.3 and Z-score >=2 or <=-2 were considered significant.
Result: PCA of clinical factors (age, BMI, and treatments) and stage distribution (Fisher's exact test) showed similar profiles between NHB and NHW BC survivors, suggesting that molecular differences in downstream analyses are unlikely to be driven by clinical or lifestyle factors. Differential expression analysis suggested that only two genes were significantly different between non-cancer NHB and NHW controls, but 92 genes, including IL8 and POLB, were significantly altered between cancer survivors. These findings suggest that the differential expression patterns are driven by cancer survivorship rather than baseline racial differences. Ninety-two genes were then analyzed with IPA, and 17 pathways were deemed significant. The Th1 and TP53 expression and degradation pathways were more active. Abasic site repair pathways were found to be inhibited in NHB survivors, consistent with our previous report.
Conclusion: Our pilot study showed that despite similar clinical profiles, NHB and NHW BC survivors exhibit distinct molecular signatures. In the future, we plan to validate these pathways and use public databases such as TCGA to evaluate how these genes affect cancer survival. Addressing these pathway differences may be key to achieving true equity in breast cancer survivorship.
利益披露 Disclosure
R. Adhikari, None.