乳腺癌組織中TCR-ζ 鏈的表達及外周血中CD8+CD28+和CD8+CD28-、CD95表達臨床意義

王艷梅　吳博　艾慶燕　趙豫鳳　楊加周　劉宇宏

[摘要] 目的 分析TCR-ζ鏈在乳腺癌組織中的表達及臨床意義。 方法 收集2015年5月～2017年8月延安大學附屬醫院（以下簡稱“我院”）經過手術及病理證實的乳腺癌患者30例（對應腫瘤組織標本，癌旁組織），收集同期來我院體檢及治療健康人群、乳腺纖維腺瘤、乳腺囊性增生病各30例作為對照，采用流式細胞技術對乳腺癌組織、癌旁組織及正常乳腺組織TCR-ζ鏈進行檢測，并且檢測乳腺癌患者血清CD8+CD28+和CD8+CD28-、CD95、TCR-ζ鏈的表達，分析乳腺癌組織、正常乳腺組織及癌旁組織TCRζ鏈的表達;外周血中各組CD8+CD28+和CD8+CD28-、CD95、TCR-ζ鏈表達對比及外周血、癌組織中TCRζ鏈表達與乳腺癌病理特征的關系。 結果 正常乳腺組織、癌旁組織、乳腺癌組織TCR-ζ鏈相對表達量差異有統計學意義（P < 0.05），其中癌旁組織、乳腺組織表達水平均高于正常乳腺組織（P < 0.05）。外周血中CD8+CD28+、CD8+CD28-、CD95、TCR-ζ鏈等免疫指標在乳腺癌、乳腺纖維腺瘤、乳腺囊性增生病四種類型患者間差異有統計學意義（P < 0.05），其中乳腺癌患者血清CD8+CD28+、CD8+CD28-、CD95、TCR-ζ鏈表達水平高于乳腺纖維腺瘤、乳腺囊性增生病及健康人群相應水平，差異有統計學意義（P < 0.05）;外周血TCR-ζ鏈表達水平與癌原發灶大小、淋巴結是否轉移、手術前后及CA125水平關系分析差異有統計學意義（P < 0.05）。 結論 檢測外周血TCR-ζ鏈對乳腺癌患者進行提前篩選、診斷或了解患者病情狀況，其在臨床上是非常有意義的指標。

[關鍵詞] 乳腺癌;TCR-ζ鏈;CD8+CD28+;CD8+CD28-;CD95

[中圖分類號] R737.9? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-7210（2019）06（b）-0097-04

Expression of TCR-ζ chain in breast cancer and the clinical significance of CD8+CD28+ and CD8+CD28- and CD95 expression in peripheral blood

WANG Yanmei1? ?WU Bo1? ?AI Qingyan1? ?ZHAO Yufeng1? ?YANG Jiazhou1? ?LIU Yuhong2

1.Department of Histology and Embryology， Medical College of Yan′an University， Shaanxi Province， Yan′an? 716000， China; 2.Department of Rheumatology and Immunology， Yan′an University Affiliated Hospital， Shaanxi Province， Yan′an? 716000， China

[Abstract] Objective To analyze the expression and clinical significance of TCR-ζ chain in breast cancer tissues. Methods Thirty patients with breast cancer confirmed by surgery and pathology in Affiliated Hospital of Yan′an University （"our hospital" for short） from May 2015 to August 2017 （corresponding to tumor tissue specimens and adjacent tissues） were collected. 30 healthy people， 30 patients with breast fibroadenoma and 30 patients with cystic hyperplasia of breast were examined and treated in our hospital during the same period as control. Flow cytometry was used. TCR-ζ chain was detected in breast cancer tissues， adjacent tissues and normal breast tissues， and the expression of serum CD8+CD28+， CD8+CD28-， CD95， TCR-ζ chain was detected in breast cancer patients. The expression of TCR-ζ chain in breast cancer tissues， normal breast tissues and adjacent tissues was analyzed. CD8+CD28+ and CD8+CD28-， CD95， TCR-ζ chain list in peripheral blood of each group was analyzed. The expression of TCR zeta chain in peripheral blood and cancer tissues was correlated with the pathological characteristics of breast cancer. Results The relative expression of TCR-ζ chain in normal breast tissue， paracancerous tissue and breast cancer tissue was significantly different （P < 0.05）. The expression of CD8+CD28+， CD8+CD28-， CD95， TCR-ζ chain in peripheral blood was higher than that in normal breast tissue （P < 0.05）. There were significant differences among the four types of adenofibroadenoma and cystic hyperplasia of breast （P < 0.05）. The expression levels of CD8+CD28+， CD8+CD28-， CD95， TCR-ζ chain in breast cancer patients were higher than those in breast fibroadenoma， cystic hyperplasia of breast and healthy people （P < 0.05）. The expression of TCR-ζ chain in peripheral blood was significantly correlated with the size of primary tumor， lymph node metastasis， pre-and post-operative levels of CA125 （P < 0.05）. Conclusion TCR-ζ chain in peripheral blood can be used to screen， diagnose and understand the condition of breast cancer patients in advance， which is a very meaningful index in clinical practice.

[Key words] Breast cancer; TCR-ζ chain; CD8+CD28+; CD8+CD28-; CD95

乳腺癌是婦科最為常見的惡性腫瘤之一，流行病學調查資料顯示，目前該病的發病率及患病率較高，如果早發現、早診斷、早治療，乳腺癌的5年生存率高達90%[1]，因此發現早期篩檢特異性指標或者診斷指標，詳細了解患者病情及免疫狀態，對于提高患者治愈率，提高患者生活質量至關重要[2-3]。TCR-ζ鏈（T cell receptor -ζ chain，CD247）是一種受體激活的蛋白酪氨酸激酶底物，當受體與配體結合后，TCR-ζ鏈發生酪氨酸磷酸化[4]，參與淋巴細胞活化信號的轉導，研究已經發現TCR-ζ鏈表達與功能改變與慢性炎癥和自身免疫性疾病密切相關，主要在T細胞的活化過程中起著作用[5]，具有將受體與細胞內信號轉導途徑連接的功能[6]，因此設想通過檢測該指標的定量表達，對于了解患者病情狀況及免疫狀況具有重要意義。……