乳腺癌患者IDO表达及活性与新辅助化疗疗效的相关性研究

赵杨; 李昉璇; 郭丰丽; 穆坤; 吴楠; 张海莲; 刘俊田

doi:10.3969/j.issn.1000-8179.2018.06.222

乳腺癌患者IDO表达及活性与新辅助化疗疗效的相关性研究

doi: 10.3969/j.issn.1000-8179.2018.06.222

赵杨^①,,
李昉璇^②,
郭丰丽^③,
穆坤^①,
吴楠^①,
张海莲^①,
刘俊田^①, ,

①.
天津医科大学肿瘤医院乳腺二科，国家肿瘤临床医学研究中心，天津市肿瘤预防重点实验室，天津市恶性肿瘤临床医学研究中心，乳腺癌防治教育部重点实验室（天津市300060）
②.
天津医科大学肿瘤医院预防科, 国家肿瘤临床医学研究中心，天津市肿瘤预防重点实验室，天津市恶性肿瘤临床医学研究中心，乳腺癌防治教育部重点实验室（天津市300060）
③.
滨州医学院附属医院甲状腺乳腺外科

基金项目:

国家自然科学基金青年项目 81502309

详细信息

作者简介:
赵杨专业方向为乳腺肿瘤临床治疗及乳腺癌化疗耐药机制等基础研究。E-mail：15369316839@163.com

通讯作者:
刘俊田 ljt641024@163.com

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出版历程
- 收稿日期: 2017-11-06
- 修回日期: 2018-03-07
- 刊出日期: 2018-03-30

The association between the expression and activity of indoleamine 2, 3-dioxygenase and the efficacy of neoadjuvant chemotherapy in patients with breast cancer

Zhao Yang^{①
,},
Li Fangxuan^②,
Guo Fengli^③,
Mu Kun^①,
Wu Nan^①,
Zhang Hailian^①,
Liu Juntian^{①
, ,}

①.
The Second Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin 300060, China
②.
The Department of Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin 300060, China
③.
The Department of Thyroidand Breast Oncology, Binzhou Medical College Affiliated Hospital, Binzhou 256600, China

Funds:

National Natural Science Foundation of the Youth Fund 81502309

More Information

Corresponding author: Juntian Liu; ljt641024@163.com

摘要

摘要: 目的分析吲哚胺2，3-双加氧酶（indoleamine 2，3-dioxygenase，IDO）在乳腺癌患者癌组织中表达及其在外周血中活性与新辅助化疗疗效的关系。方法收集2015年9月至2016年12月天津医科大学肿瘤医院53例行新辅助化疗乳腺癌患者的肿瘤穿刺标本和血液标本，采用免疫组织化学法及高效液相色谱法检测癌组织中IDO表达及外周血中色氨酸（tryptophan，Trp）、犬尿氨酸（kynurenine，Kyn）浓度与IDO活性，分析IDO表达及活性与化疗疗效的相关性。结果新辅助化疗前乳腺癌组织中IDO表达与临床T分期（P=0.006）、N分期（P=0.020）、临床分期（P=0.045）及ER状态（P=0.014）有关。新辅助化疗前外周血中IDO高活性伴随癌组织中IDO高表达（P=0.004），并与临床T分期（P=0.019）及N分期（P=0.047）有关。单因素分析显示新辅助化疗临床疗效与化疗前临床T分期（P=0.049）、ER状态（P=0.025）及分子分型（P=0.014）有关；病理完全缓解（pathologic complete response，pCR）与化疗前临床T分期（P=0.014）有关。更重要的是新辅助化疗临床疗效及pCR均与化疗前IDO表达及活性有关（均P < 0.05）。多因素分析显示新辅助化疗前外周血中IDO活性是影响pCR的唯一独立因素（P=0.032）。结论新辅助化疗前乳腺癌组织中IDO表达和外周血中IDO活性与化疗疗效相关，可以为临床预测化疗是否敏感提供一定信息。
- 乳腺癌 /
- 吲哚胺2，3-双加氧酶 /
- 新辅助化疗 /
- 化疗疗效 /
- 病理完全缓解
Abstract: Objective To investigate the association between indoleamine 2, 3-dioxygenase (IDO) expression in tumor tissue, its peripheral blood activity, and the efficacy of neoadjuvant chemotherapyin patients with breast cancer. Methods Immunohistochemistry (IHC) and high-performance liquid chromatography (HPLC) were used to measure IDO protein expression in tumor tissue, and kynurenine (Kyn), tryptophan (Trp), and IDO activity (Kyn/Trp) in peripheral blood before neoadjuvant chemotherapy in 53 patients with breast cancer from Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2016. The correlations between the expression and activity of IDO and the efficacy of chemotherapy were analyzed. Results In tumor tissue, IDO expressionbefore neoadjuvant chemotherapy was related to clinical tumor stages (P=0.006), node stages (P=0.020), clinical stages (P=0.045), and estrogen receptor (ER) status (P=0.014). High IDO activity before neoadjuvant chemotherapy in peripheral blood was associated with high IDO expression in tumor tissue (P=0.004), and was also correlated with clinical tumor stages (P=0.019) and node stages (P=0.047). Univariate analysis showed that the clinical efficacy of neoadjuvant chemotherapy was associated with pre-chemotherapeutic clinical tumor stages (P=0.049), ER status (P=0.025), and molecular subtype (P=0.014), while pathologic complete response (pCR) was related to pre-chemotherapeutic clinical tumor stages (P=0.014). Importantly, the clinical efficacy of neoadjuvant chemotherapy and pCR were both related to IDO expression and activity before chemotherapy (all P < 0.05). Multivariate analysis showed that pre-chemotherapeutic IDO activity in peripheral blood was the only independent factor that affected pCR (P=0.032). Conclusions Tumor tissue IDO expression and peripheral blood IDO activity before chemotherapy were associated with chemotherapy efficacy, and could provide promising information for the clinical prediction of chemotherapy sensitivity.
- breast cancer /
- indoleamine 2, 3-dioxygenase /
- neoadjuvant chemotherapy /
- chemotherapy efficacy /
- pathologic complete response

HTML全文

图 1 免疫组织化学法检测乳腺癌组织中IDO表达（SP×400）

A：IDO（-）低表达；B：IDO（+）低表达；C：IDO（++）高表达；D：IDO（+++）高表达

下载: 全尺寸图片幻灯片

图 2 高效液相色谱法检测乳腺癌患者外周血中IDO活性

A：IDO高活性；B：IDO低活性；↓：Kyn波峰；↓↓：Trp波峰

下载: 全尺寸图片幻灯片

图 3 乳腺癌组织中IDO表达与外周血中IDO活性的关系

^**：P < 0.01

下载: 全尺寸图片幻灯片

表 1 53例乳腺癌患者新辅助化疗前癌组织中IDO表达及外周血中IDO活性与临床病理特征的相关性

表 2 53例乳腺癌患者新辅助化疗前癌组织中IDO表达及外周血中IDO活性和化疗疗效的关系

表 3 53例乳腺癌患者新辅助化疗疗效的单因素分析

表 4 乳腺癌患者新辅助化疗疗效的多因素二元Logistic回归分析

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