摘要
目的观察外周血CD14~+单核细胞中人白细胞DR抗原(CD14~+/HLA-DR~+)表达水平及纤维蛋白原(Fib)浓度变化,探讨炎性标记物检测对肺癌患者预后的评估价值。方法应用流式细胞术及免疫比浊法检测CD14~+/HLA-DR~+水平及Fib浓度,并分析其与肿瘤病理特征及无病生存期的相关性。结果肺癌外周血中CD14~+/HLA-DR~+的水平较对照组明显降低(t=-3.174,P <0.01),而Fib浓度较对照组明显升高(t=3. 46,P <0. 01);肺癌患者CD14~+/HLA-DR~+水平与Fib浓度呈负相关性(r=-0.515,P <0. 01)。患者治疗前CD14~+/HLA-DR~+水平与吸烟史、TNM分期、淋巴结转移有关(P <0. 05),Fib浓度与吸烟史、TNM分期、淋巴结转移、肿块大小、脉管癌栓及病理类型等有关(P <0. 05)。在肺癌中,CD14~+/HLA-DR~+低表达水平组和(或) Fib高浓度组的患者无病生存期明显降低(P <0. 01); Cox比例风险模型多因素分析显示,TNM分期及CD14~+/HLA-DR~+水平是影响肺癌患者无病生存期的独立预后因素(P <0. 01)。结论 CD14~+/HLA-DR~+水平及Fib浓度可作为判断肺癌恶性程度的指标; TNM分期及CD14~+/HLA-DR~+水平是影响肺癌患者无病生存期的独立预后因素。
Objective To study the detection of inflammatory markers on the prognosis of patients with lung cancer through detecting the expression of human leukocyte antigen DR( CD14~+/HLA-DR~+) in CD14~+monocytes of peripheral blood and the changes of fibrinogen( Fib) concentrations. Methods The levels of CD14~+/HLA-DR~+monocytes and plasma Fib were analyzed by flow cytometry and immunoturbidimetry; and its relationship with clinicopathologic characteristics and prognostic for disease-free survival( DFS) were analyzed. Results The levels of CD14~+/HLA-DR~+monocytes in lung cancer patients were significantly lower than those in healthy controls( t =-3. 174,P < 0. 01),while the Fib levels were significantly higher than those in controls( t = 3. 46,P < 0. 01); the levels of CD14~+/HLA-DR~+monocytes was negatively correlated with Fib concentrations in patients with lung cancer( r =-0. 515,P < 0. 01). The levels of CD14~+/HLA-DR~+monocytes before treatment were related with smoking history,TNM stage,and lymph node metastasis( P < 0. 05); Fib concentration was correlated with smoking history,TNM stage,lymph node metastasis,tumor size,vascular tumor thrombus and different histological classifications( P < 0. 05). The low level of CD14~+/HLA-DR~+monocytes and/or hyperfibrinogenemia had a worse prognostic significance to patients' disease-free survival( DFS) time( P < 0. 01); Cox multivariate regression analysis revealed that TNM stage and CD14~+/HLA-DR~+monocytes level were independent predictive factors for decreased DFS( P <0. 01). Conclusion The level of CD14~+/HLA-DR~+monocytes and Fib concentration can be promising biomarkers for evaluating the progression of lung cancer; TNM stage and CD14~+/HLA-DR~+monocytes level are independent prognositic factors affecting DFS in lung cancer patients.
引文
[1] BottaC,Barbieri V,Ciliberto D,et al. Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients[J]. Cancer Biol Ther,2013,14(6):469-475.
[2]周筱琼,严静,于小妹,等.老年脓毒症患者活化淋巴细胞的表达及意义[J].中国卫生检验杂志,2010,20(12):3090-3093.
[3] Castellheim A,Brekke OL,Espevik T,et al. Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis[J]. Scand J Immunol,2009,69(6):479-491.
[4]张敏,杨晓,徐笑红,等. C反应蛋白、纤维蛋白原及血小板与肺癌患者预后的关系研究[J].中国卫生检验杂志,2016,26(9):1273-1275.
[5] Volk HD,Reinke P,D9cke WD. Clinical aspects:from systemic inflammation to ‘immunoparalysis'[J]. Chem Immunol,2000,74:162-177.
[6]杨晓,张腊红,洪理泉,等.血小板、纤维蛋白原、前列腺特异抗原联合检测在前列腺癌诊断中的意义[J].中国卫生检验杂志,2017,27(14):2031-2033.
[7] Chornoguz O,Gapeev A,O'Neill MC,et al. Major histocompatibility complex class II+invariant chain negative breast cancer cells present unique peptides that activate tumor-specific T cells from breast cancer patients[J]. Mol Cell Proteomics,2012,11(11):1457-1467.
[8] Seliger B,Kloor M,Ferrone S. HLA class II antigen-processing pathway in tumors:Molecular defects and clinical relevance[J].Oncoimmunology,2017,6(2):e1171447.
[9] Yamashita H,Kitayama J,Taguri M,et al. Effect of preoperative hyperfibrinogenemia on recurrence of colorectal cancer without a systemic inflammatory response[J]. World J Surg,2009,33(6):1298-1305.
[10] Yu X,Hu F,Yao Q,et al. Serum fibrinogen levels are positively correlated with advanced tumor stage and poor survival in patients with gastric cancer undergoing gastrectomy:a large cohort retrospective study[J]. BMC Cancer,2016,16:480.
[11] Mant TG,Borozdenkova S,Bradford DB,et al. Changes in HLADR expression,cytokine production and coagulation followingendotoxin infusion in healthy human volunteers[J]. Int Immuno pharmacol,2008,8(5):701-707.
[12] Qian BZ,Pollard JW. Macrophage diversity enhances tumor progression and metastasis[J]. Cell,2010,141(1):39-51.
[13] Corthay A. CD4+T cells cooperate with macrophages for specific elimination of MHC class II-negative cancer cells[J]. Adv Exp Med Biol,2007,590:195-208.
[14] Haabeth OA,Tveita AA,Fauskanger M,et al. How do CD4+T cells detect and eliminate tumor cells that either lack or express MHC class II molecules?[J]. Front Immunol,2014,5:174.
[15]卢国光,侯芳妮,袁远,等.凝血指标与宫颈恶性肿瘤相关性分析[J].中国卫生检验杂志,2017,27(18):2614-2616.