Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
Population Studies and Disparities Research Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, United States of America.
PLoS One. 2020 Apr 16;15(4):e0231712. doi: 10.1371/journal.pone.0231712. eCollection 2020.
Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets.
We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 494 TN tumors using four publically available data sets. Meta-analyses were performed using summary statistics from the four validation results.
In the Detroit AA cohort, CLCA2 [Hazard ratio (HR) = 1.56, 95% confidence interval (CI) 1.31-1.86, nominal p = 5.1x10-7, FDR p = 0.014], SPIC [HR = 1.47, 95%CI 1.26-1.73, nominal p = 1.8x10-6, FDR p = 0.022], and MIR4311 [HR = 1.57, 95% CI 1.31-1.92, nominal p = 2.5x10-5, FDR p = 0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. CLCA2 was also associated with increased risk of death in the validation cohorts [HR = 1.14, 95% CI 1.05-1.24, p = 0.038, p-heterogeneity = 0.88].
We identified CLCA2 as a potential prognostic marker for TNBC in AA women.
与白人相比，非裔美国（AA）女性被诊断为三阴性乳腺癌（TNBC）的可能性要高出两倍，这是一种侵袭性乳腺癌亚型，与预后不良有关。目前尚无针对 TNBC 的常规靶向临床治疗方法；因此，迫切需要确定预后标志物和潜在的治疗靶点。
我们评估了来自底特律的 155 例未经治疗的 AA 女性 TN 肿瘤中的 27016 个基因的表达。使用 Cox 比例风险模型评估与生存的相关性，该模型调整了分期和诊断时的年龄，并使用错误发现率校正了 p 值。我们的验证样本由来自四个公共数据集的 494 个 TN 肿瘤组成。使用四个验证结果的汇总统计数据进行了荟萃分析。
在底特律 AA 队列中，CLCA2 [风险比（HR）= 1.56，95%置信区间（CI）1.31-1.86，名义 p = 5.1x10-7，FDR p = 0.014]、SPIC [HR = 1.47，95%CI 1.26-1.73，名义 p = 1.8x10-6，FDR p = 0.022]和 MIR4311 [HR = 1.57，95%CI 1.31-1.92，名义 p = 2.5x10-5，FDR p = 0.022]表达与总生存相关。进一步调整治疗和乳腺癌特异性生存分析并没有显著改变效应估计。CLCA2 也与验证队列中死亡风险增加相关 [HR = 1.14，95%CI 1.05-1.24，p = 0.038，p 异质性 = 0.88]。
我们确定 CLCA2 是非裔美国 TNBC 女性的潜在预后标志物。
