Low TINAGL1 expression is a marker for poor prognosis in breast cancer
Low TINAGL1 expression is a marker for poor prognosis in breast cancer
复制标题
DOI：
10.1007/s00432-022-04394-3
复制
发表时间：
2022-10
影响因子：
3.6
通讯作者：
Akiko Kato;N. Kondo;Yumi Wanifuchi-Endo;T. Fujita;Tomoko Asano;T. Hisada;Y. Uemoto;M. Terada
中科院分区：
文献类型：
--
作者：
Akiko Kato;N. Kondo;Yumi Wanifuchi-Endo;T. Fujita;Tomoko Asano;T. Hisada;Y. Uemoto;M. Terada
目的：研究发现小管间质性肾炎抗原样1 （TINAGL1）可抑制三阴性乳腺癌的肿瘤转移和生长。我们的目的是通过长期随访来确定tinagl1表达与乳腺癌患者临床病理因素和预后的关系。方法选取599例在我院连续行手术获得组织标本的原发性浸润性乳腺癌患者作为研究对象。使用TaqMan实时PCR系统检测所有599个组织标本中TINAGL1mRNA的表达。在299例可用的组织标本中进一步检测tinagl1蛋白的表达，进行免疫组织化学染色。采用Kaplan-Meier法和Cox比例风险模型进行生存分析。结果中位随访期为12.0年。在所有患者中，lowTINAGL1mRNA的表达与低表达的患者相比，与较短的无病生存期（DFS）和总生存期相关（P= 0.003和P= 0.01）。此外，低tinagl1mrna表达的激素受体阳性/人表皮生长因子受体2阴性乳腺癌患者预后更差。多因素分析发现，低tinagl1mrna表达结合淋巴结阳性是侵袭性乳腺癌患者DFS的独立预后不良因素（HR 1.41; 95% CI 1.02-1.96；P= 0.036）。TINAGL1mRNA的表达也随绝经状态而变化，在绝经前患者中，低TINAGL1mRNA的表达与预后不良呈正相关，而在绝经后患者中则没有。结论TINAGL1可能是一种有前景的候选乳腺癌生物标志物和治疗靶点。
PurposeTubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations ofTINAGL1expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up.MethodsA total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study.TINAGL1mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system.TINAGL1protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan–Meier method and Cox proportional hazards models.ResultsThe median follow-up period was 12.0 years. In the total patients, lowTINAGL1mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P= 0.003 andP= 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with lowTINAGL1mRNA expression had a worse prognosis. Multivariate analysis identified lowTINAGL1mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02–1.96;P= 0.036).TINAGL1mRNA expression also varied with menopausal status, with lowTINAGL1mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients.ConclusionOur findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.