血清神經(jīng)生長因子及細胞免疫水平在乳腺癌中的表達及其與臨床病理特征的相關(guān)性

王文慧 溫媛媛 陳豪

[摘要] 目的 探討血清神經(jīng)生長因子（NGF）及細胞免疫水平在乳腺癌患者中的表達及其與臨床病理特征的相關(guān)性。 方法 選擇2015年3月～2018年2月在杭州市婦產(chǎn)科醫(yī)院及浙江省舟山醫(yī)院確診的乳腺癌患者49例，設(shè)為觀察組;選擇同期入院的乳腺良性疾病患者45例，設(shè)為對照組;選擇同期入院健康體檢女性47名，設(shè)為正常組。采用酶聯(lián)免疫吸附試驗測定各組NGF表達水平;采用流式細胞儀測定各組CD3+、CD4+、CD8+及CD4+/CD8+水平;記錄并統(tǒng)計患者臨床病理資料，分析各組和觀察組乳腺癌不同臨床病理資料的NGF、細胞免疫水平;采用Pearson分析NGF、細胞免疫水平與乳腺癌患者臨床病理資料的相關(guān)性。 結(jié)果 三組NGF、細胞免疫水平比較，差異均有統(tǒng)計學(xué)意義（P < 0.05）。觀察組NGF水平高于對照組與正常組，且對照組NGF水平高于正常組，差異均有統(tǒng)計學(xué)意義（P < 0.05）。觀察組CD3+、CD4+及CD4+/CD8+水平低于對照組與正常組，CD8+水平高于對照組與正常組，差異均有統(tǒng)計學(xué)意義（P < 0.05）;對照組與正常組CD3+、CD4+、CD8+及CD4+/CD8+水平比較，差異無統(tǒng)計學(xué)意義（P > 0.05）。乳腺癌組織中NGF、CD3+、CD4+、CD8+及CD4+/CD8+水平在年齡、病理組織學(xué)類型方面比較，差異無統(tǒng)計學(xué)意義（P > 0.05）;乳腺癌組織中NGF、CD3+、CD4+、CD8+及CD4+/CD8+水平在腫瘤最大徑、病理分級、分化程度及淋巴結(jié)轉(zhuǎn)移方面比較，差異均有統(tǒng)計學(xué)意義（P < 0.05）;Pearson相關(guān)性分析顯示：NGF、CD8+水平與腫瘤最大徑、病理分級、分化程度及淋巴結(jié)轉(zhuǎn)移呈正相關(guān)（P < 0.05）;CD3+、CD4+及CD4+/CD8+水平與腫瘤最大徑病理分級、分化程度及淋巴結(jié)轉(zhuǎn)移呈負相關(guān)（P < 0.05）。 結(jié)論 NGF在乳腺癌患者中呈高表達，導(dǎo)致機體細胞免疫水平下降，且二者表達水平與病理特征具有相關(guān)性，加強NGF及細胞免疫水平測定能評估患者疾病嚴重程度，指導(dǎo)臨床治療。

[關(guān)鍵詞] 血清神經(jīng)生長因子;細胞免疫水平;乳腺癌;病理特征;相關(guān)性;酶聯(lián)免疫吸附試驗;流式細胞儀

[中圖分類號] R737.9 ? ? ? ? ?[文獻標識碼] A ? ? ? ? ?[文章編號] 1673-7210（2020）04（b）-0088-05

Expression of serum nerve growth factor and cellular immunity in breast cancer and its correlation with clinicopathological feature

WANG Wenhui1 ? WEN Yuanyuan2 ? CHEN Hao1

1.Department of Pathology， Hangzhou Maternity Hospital， Zhejiang Province， Hangzhou ? 310008， China; 2.Pathological Diagnosis Center， Zhejiang Zhoushan Hospital， Zhejiang Province， Zhoushan ? 316021， China

[Abstract] Objective To investigate the expression of serum nerve growth factor （NGF） and cellular immunity in breast cancer patients and its correlation with clinicopathological feature. Methods A total of 49 breast cancer patients diagnosed in Hangzhou Maternity Hospital and Zhejiang Zhoushan Hospital from March 2015 to February 2018 were selected as the observation group. A total of 45 patients with benign breast disease who were hospitalized at the same time were selected as the control group. A total of 47 female patients with physical examination at the same time were selected as the normal group. The expression levels of NGF in each group were determined by enzyme-linked immunosorbent assay. The levels of CD3+， CD4+， CD8+ and CD4+/CD8+ in each group were determined by flow cytometry. The clinicopathological data of the patients were recorded and counted. The levels of NGF and cellular immunity in each group and the levels of NGF and cellular immunity in different clinicopathological data of breast cancer in the observation group were analyzed. The correlation between NGF， cellular immunity level and clinicopathological data of breast cancer patients was analyzed by Pearson analysis. Results The levels of NGF and cellular immunity in the three groups were statistically significant （P < 0.05）. The level of NGF in the observation group was higher than that in the control group and the normal group， and the level of NGF in the control group was higher than that in the normal group， with statistically significant differences （P < 0.05）. The levels of CD3+， CD4+ and CD4+/CD8+ in the observation group were lower than those in the control group and the normal group， and the level of CD8+ was higher than that in the control group and the normal group， with statistically significant differences （P < 0.05）. There was no significant difference in the levels of CD3+， CD4+， CD8+ and CD4+/CD8+ between the control group and the normal group （P > 0.05）. The levels of NGF， CD3+， CD4+， CD8+ and CD4+/CD8+ in breast cancer tissues were not statistically significant differences in terms of age and histopathological type （P > 0.05）. The levels of NGF， CD3+， CD4+， CD8+ and CD4+/CD8+ in breast cancer tissues were compared in terms of tumor maximum diameter， pathological grading， differentiation degree and lymph node metastasis， with statistically significant differences （P < 0.05）. The Pearson correlation analysis results showed that the NGF and CD8+ levels were positively correlated with the maximum tumor diameter， pathological grading， differentiation degree and lymph node metastasis （P < 0.05）. The levels of CD3+， CD4+ and CD4+/CD8+ were negatively correlated with the maximum tumor diameter， pathological grading， differentiation degree and lymph node metastasis （P < 0.05）. Conclusion The high expression of NGF in breast cancer patients leads to the decline of cellular immunity level in the body， and the expression level of both is correlated with the pathology feature. Strengthening the determination of NGF and cellular immunity level can assess the severity of the disease in patients and guide clinical treatment.

乳腺癌的發(fā)生發(fā)展是一個多因素過程，常伴有細胞免疫水平的變化[16-17]。研究表明[18-19]，腫瘤患者外周血腫細胞免疫水平常呈低表達。CD4+T細胞能調(diào)控局部炎癥與細胞毒相關(guān)的免疫應(yīng)答，能促進機體產(chǎn)生抗體;此外，CD4+T細胞還能活化自然殺傷細胞與巨噬細胞，提高巨噬細胞的殺傷能力;CD8+T細胞毒性相對較輕，在殺死腫瘤細胞中發(fā)揮了重要的作用。研究表明[20-21]，細胞免疫對于腫瘤免疫反應(yīng)的抑制能在淋巴組織中表現(xiàn)，能種植效應(yīng)細胞活化階段，改變腫瘤的微環(huán)境，從而干擾機體正常的抗腫瘤免疫應(yīng)答，抑制腫瘤細胞的清除。乳腺癌患者中細胞免疫水平受影響因素較多，包括腫瘤的分期、腫瘤大小、分化程度等。本研究中，分析結(jié)果顯示：NGF、CD8+水平與腫瘤最大徑、病理分級、分化程度及淋巴結(jié)轉(zhuǎn)移呈正相關(guān)（P < 0.05）;CD3+、CD4+及CD4+/CD8+水平與腫瘤最大徑、病理分級、分化程度及淋巴結(jié)轉(zhuǎn)移呈負相關(guān)（P < 0.05）。可見乳腺癌患者中細胞免疫水平與病理表現(xiàn)存在相關(guān)性。為了提高乳腺癌患者診斷、治療效果，可加強患者NGF和細胞免疫水平測定，評估患者疾病嚴重程度;對于確診的乳腺癌患者盡早給予手術(shù)、放化療等治療，且治療過程中加強患者NGF和細胞免疫水平測定能評估患者預(yù)后，可以視檢測結(jié)果調(diào)整治療方案，使得患者的治療更具科學(xué)性[22]。

綜上所述，NGF在乳腺癌患者中呈高表達，導(dǎo)致機體細胞免疫水平下降，且二者表達水平與病理表現(xiàn)具有相關(guān)性，加強NGF及細胞免疫水平測定能評估患者疾病嚴重程度，指導(dǎo)臨床治療。

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（收稿日期：2019-08-21 ?本文編輯：顧家毓）