Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes.
Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes.
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重新定义了乳腺癌的预后因素：YB-1比雌激素受体或HER-2在所有肿瘤亚型中比雌激素受体或HER-2更强的预测指标。
DOI：
10.1186/bcr2156
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Dunn SE
中科院分区：
文献类型：
--
作者：
Habibi G;Leung S;Law JH;Gelmon K;Masoudi H;Turbin D;Pollak M;Nielsen TO;Huntsman D;Dunn SE
基因表达分析用于对乳腺癌进行分型，以便识别最具侵袭性的肿瘤，但将其转化为临床实践可能很麻烦。我们的目标是开发一种通用的生物标志物，用于区分所有乳腺癌亚型的高风险患者。我们以前报道过，Y-box结合蛋白-1（YB-1）是一种转录/翻译因子，是490例乳腺癌患者队列中预后不良的标志物，但该研究规模不够大，无法对癌症进行分型。因此，我们通过评估4，049例病例，研究了YB-1是否识别出所有肿瘤亚型中无复发生存率降低或乳腺癌特异性生存率（BCSS）降低的患者。肿瘤组织微阵列，代表4,049例浸润性乳腺癌，随访20年，通过雌激素受体，孕激素受体或HER-2的表达谱进行亚型分析。然后，我们讨论了YB-1表达是否识别出复发风险较高和/或BCSS较低的患者。我们发现YB-1是整个队列和所有乳腺癌亚型中复发（P < 2.5 × 10-20）和生存不良（P < 7.3 × 10-26）的高度预测生物标志物。如果YB-1表达，淋巴结阳性或淋巴结阴性癌症患者更有可能死于疾病。考克斯回归模型进一步证实了这一点，该模型显示，它与复发和生存率差显著相关，且与亚型无关（复发患者，风险比= 1.28，P < 8 × 10-3;所有患者，风险比= 1.45，P < 6.7 × 10-7）。此外，YB-1作为复发和生存的预后标志物上级雌激素受体和HER-2。对于一部分原本认为低危而未接受化疗的患者，YB-1提示生存率低（P < 7.1 × 10 - 17）。同样，YB-1预测他莫昔芬治疗患者的BCSS降低（P = 0.001）;在这种情况下，考克斯回归模型再次证明它是一个独立的生物标志物，表明生存率低（风险比= 1.70，P = 0.022）。YB-1的表达普遍识别所有乳腺癌亚型的高风险患者，以及可能需要更积极治疗的情况。因此，我们认为YB-1可能会重新定义高危乳腺癌，从而为个体化治疗创造机会。
Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previously reported that Y-box binding protein-1 (YB-1), a transcription/translation factor, was a marker of poor prognosis in a cohort of 490 patients with breast cancer, but the study was not large enough to subtype the cancers. We therefore investigated whether YB-1 identifies patients at risk for either reduced relapse free survival or decreased r breast cancer specific survival (BCSS) across all tumor subtypes by evaluating 4,049 cases. Tumor tissue microarrays, representing 4,049 cases of invasive breast cancers with 20 years of follow up, were subtyped by the expression profiles of estrogen receptor, progesterone receptor, or HER-2. We then addressed whether YB-1 expression identified patients at higher risk for relapse and/or lower BCSS. We found YB-1 to be a highly predictive biomarker of relapse (P < 2.5 × 10-20) and poor survival (P < 7.3 × 10-26) in the entire cohort and across all breast cancer subtypes. Patients with node-positive or node-negative cancer were more likely to die from the disease if YB-1 was expressed. This was further substantiated using a Cox regression model, which revealed that it was significantly associated with relapse and poor survival in a subtype independent manner (relapse patients, hazard ratio = 1.28, P < 8 × 10-3; all patients, hazard ratio = 1.45, P < 6.7 × 10-7). Moreover, YB-1 was superior to estrogen receptor and HER-2 as a prognostic marker for relapse and survival. For a subset of patients who were originally considered low risk and were therefore not given chemotherapy, YB-1 was indicative of poor survival (P < 7.1 × 10 -17). Likewise, YB-1 was predictive of decreased BCSS in tamoxifen-treated patients (P = 0.001); in this setting a Cox regression model once again demonstrated it to be an independent biomarker indicating poor survival (hazard ratio = 1.70, P = 0.022). Expression of YB-1 universally identifies patients at high risk across all breast cancer subtypes and in situations where more aggressive treatment may be needed. We therefore propose that YB-1 may re-define high-risk breast cancer and thereby create opportunities for individualized therapy.
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DOI：
10.1186/bcr1370
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Shadeo A;Lam WL
通讯作者：
Lam WL
影响因子：
3.8
作者：
Rajput, Ashish B.;Turbin, Dmitry A.;Cheang, Maggie C. U.;Voduc, David K.;Leung, Sam;Gelmon, Karen A.;Gilks, C. Blake;Huntsman, David G.
通讯作者：
Huntsman, David G.
影响因子：
14.9
作者：
Makino, Y;Ohga, T;Kohno, K
通讯作者：
Kohno, K
影响因子：
4.8
作者：
Uramoto, H;Izumi, H;Kohno, K
通讯作者：
Kohno, K
影响因子：
11.2
作者：
Fujii, Teruhiko;Kawahara, Akihiko;Kage, Masayoshi
通讯作者：
Kage, Masayoshi