TrkC表达可预测乳腺浸润性导管癌的良好临床结局，且与NT-3表达无关。

TrkC expression predicts favorable clinical outcome in invasive ductal carcinoma of breast independent of NT-3 expression.

作者信息

Zhang Wei, Lin Zhi-Chun, Zhang Tong-Xian, Liu Shan, Liu Xia, Liu Jun-Jun, Niu Yun

机构信息

Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital and National Clinical Research Center of Cancer West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China.

Department of Nuclear Medicine, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces Chenglin Road, Hedong District, Tianjin 300162, China.

出版信息

Am J Cancer Res. 2014 Nov 19;4(6):811-23. eCollection 2014.

PMID:25520870

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4266714/

Abstract

BACKGROUND

TrkC, a member of neurotrophin receptor family, functions not only as an oncogene, but also act as a tumor suppressor via a manner of dependence receptor in human malignant tumors. Little is known on the action of TrkC for the clinical prognosis and the progression of breast cancer according to the availability of its ligand NT-3. We sought to investigate the prognostic relevance of NT-3-TrkC axis in breast cancer and estimate its role during the process of breast cancer progression.

METHODS

236 cases of invasive ductal carcinoma (IDC), 60 pure ductal carcinoma in situ (DCIS) and 30 normal breast tissue (NBT) between 2004 and 2005 were included in the study. Spearman's rank correlation test was used to analyze the association of NT-3-TrkC expression and breast cancer progression. The Kaplan-Meier method and Cox proportional hazards model were performed to identify the relevant prognostic factors.

RESULTS

50.4% IDC tumors displayed absent or low TrkC expression, while 49.6% was high TrkC expression. TrkC expression was negatively associated with lymph node metastasis (P = 0.029) and tumor proliferation (P = 0.015). Patients with lower TrkC expressing tumors had a higher risk of recurrence (odds ratio, 0.401; 95% confidence interval, 0.207-0.778; P = 0.007). The layered analysis indicated that patients with high TrkC expression tumors had a favor disease-free survival whether NT-3 and TrkC were co-expressed or solitarily expressed in the tumor (P = 0.000). NT-3 was demonstrated to be not a predictor of IDC patients' prognosis. But NT-3 expression was inversely correlated with the progression of breast cancer (r = -0.341, P = 0.000), since more IDC tumors showed high NT-3 expression than DCIS tumors (51.7% vs. 25.9%), while no NBT showed high NT-3 expression, as well.

CONCLUSION

The study indicates TrkC expression reduces tumor relapse independent of NT-3 availability in the IDC. Elevated NT-3 expression contributes to the progression of breast cancer.

摘要

背景

神经营养因子受体家族成员TrkC不仅作为一种癌基因发挥作用，在人类恶性肿瘤中还可通过依赖受体的方式充当肿瘤抑制因子。关于TrkC根据其配体NT-3的可获得性对乳腺癌临床预后及进展的作用，目前所知甚少。我们旨在研究NT-3-TrkC轴在乳腺癌中的预后相关性，并评估其在乳腺癌进展过程中的作用。

方法

本研究纳入了2004年至2005年间的236例浸润性导管癌（IDC）、60例纯原位导管癌（DCIS）和30例正常乳腺组织（NBT）。采用Spearman等级相关检验分析NT-3-TrkC表达与乳腺癌进展的相关性。运用Kaplan-Meier法和Cox比例风险模型确定相关预后因素。

结果

50.4%的IDC肿瘤表现为TrkC表达缺失或低表达，而49.6%为TrkC高表达。TrkC表达与淋巴结转移（P = 0.029）及肿瘤增殖（P = 0.015）呈负相关。TrkC表达较低的肿瘤患者复发风险较高（比值比，0.401；95%置信区间，0.207 - 0.778；P = 0.007）。分层分析表明，无论NT-3和TrkC在肿瘤中是共表达还是单独表达，TrkC高表达肿瘤的患者无病生存期较好（P = 0.000）。NT-3被证明不是IDC患者预后的预测指标。但NT-3表达与乳腺癌进展呈负相关（r = -0.341，P = 0.000），因为显示NT-3高表达的IDC肿瘤比DCIS肿瘤更多（51.7%对25.9%），而正常乳腺组织中也没有显示NT-3高表达的情况。