CD14~+/HLA-DR~+及纤维蛋白原在肺癌中的表达及其与预后的关系
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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.
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
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[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.
[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.
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