Yang Fang, Cao Lulu, Sun Zijia, Jin Juan, Fang Hehui, Zhang Wenwen, Guan Xiaoxiang
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
Int J Biol Sci. 2016 Dec 7;12(12):1568-1577. doi: 10.7150/ijbs.16874. eCollection 2016.
Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44/CD24, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44/CD24 and ALDH1A1 was significantly associated with worse PFS ( = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC.
三阴性乳腺癌(TNBC)是一种侵袭性强、临床预后差的肿瘤亚型,因为缺乏有效的治疗方法。乳腺癌干细胞(BCSCs)被认为具有肿瘤起始特性,但它们的存在是否导致TNBC侵袭性增加和预后不良仍不清楚。此外,乳腺癌表现出频繁的肿瘤间和肿瘤内异质性,这增加了诊断和预测预后的复杂性。在此,我们研究了88例TNBC病例中BCSC标志物CD44/CD24、醛脱氢酶家族1成员A1(ALDH1A1)和CD133的临床相关性及预后价值。我们发现少数患者的BCSC标志物表达存在空间异质性,以下将其定义为肿瘤内干性异质性(ITSH)。单独的任何BCSC标志物或ITSH与无进展生存期(PFS)之间均无显著相关性。有趣的是,CD44/CD24和ALDH1A1联合的BCSC表型与较差的PFS显著相关(P = 0.009)。进一步的分层分析显示,这种联合的BCSC表型在某些亚组中是PFS的独立预后因素。总之,我们证明了TNBC中存在ITSH,发现ITSH以及单个BCSC标志物与生存率无显著相关性,而综合分析BCSC标志物可提高预后价值。我们的研究结果可能会改善TNBC的预后指标。