弥漫大B细胞淋巴瘤患者外周血CD14~+单核细胞TF、VEGF表达的临床意义
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摘要
目的:探讨弥漫大B细胞淋巴瘤(DLBCL)患者外周血CD14~+单核细胞组织因子(TF)和血管内皮生长因子(VEGF)表达的临床意义。方法:应用流式细胞术检测41例DLBCL患者(病例组)化疗前、4个疗程化疗后以及20例健康体检者(对照组)外周血CD14~+单核细胞TF和VEGF的表达水平,分析TF和VEGF表达与国际预后指数(IPI)、短期疗效以及生存的关系。结果:病例组外周血CD14~+单核细胞TF、VEGF的表达水平显著高于对照组(P <0.01),2者表达呈正相关(r=0.755,P <0.01)。不同性别、年龄、亚型病例组CD14~+单核细胞TF、VEGF表达水平均无明显差异(P> 0.05)。具有预后危险因素患者CD14~+单核细胞TF、VEGF表达水平与不具有预后危险因素者比较均明显增高(P <0.05)。随着IPI指数的增高,病例组CD14~+单核细胞TF和VEGF表达均有递增趋势(P <0.01)。缓解组化疗前CD14~+单核细胞TF、VEGF表达水平低于未缓解组(P均<0.01);化疗后缓解组CD14~+单核细胞TF、VEGF表达水平均低于化疗前水平(P <0.01),未缓解组TF和VEGF表达水平较化疗前变化不大(P> 0.05)。TF和VEGF低表达组生存状况均优于TF、VEGF高表达组(P <0.05)。结论:DLBCL患者外周血CD14~+单核细胞高表达TF和VEGF,与国际预后指数、疗效、生存相关,对评估疗效、预后具有参考意义。
Objective: To investigate the clinical significance of tissue factor(TF) and vascular endothelial growth factor(VEGF) expression on peripheral blood CD14 positive monocytes in patients with diffuse large B cell lymphoma(DLBCL). Methods: The expressions of TF and VEGF on peripheral CD14~+ monocytes in 41 patients with DLBCL(DLBCL group) before chemotherapy and after 4 chemotherapeutic courses, and in 20 healthy subjects(control group) were detected by flow cytometry respectively, meanwhile, the relationship of the expression of TF and VEGF with international prognostic indexes(IPI) and short-term effects were analysed. Results: The expression levels of TF and VEGF on peripheral CD14~+ monocytes in DLBCL group were significantly higher than those in control group(P<0.01), and a positive correlation was found between the two groups(r=0.755, P<0.01). The expression of TF and VEGF on CD14~+ monocytes in patients with prognostic risk factors significantly increased as compared with those in patients without prognostic risk factors(P<0.05), but there were no significant differences of TF and VEGF expressions on CD14~+ monocytes in DLBCL group with different sex, age, subtypes(P>0.05). As compared with patients without prognostic risk factors, the expression levels of TF and VEGF on CD14~+ monocytes of patients with prognostic risk factors significantly increased(P<0.05). The expression of TF and VEGF on CD14~+ monocytes in DLBCL group showed an increasing tendency along with the increase of IPI index(P<0.01). The expression levels of TF and VEGF on CD14~+ monocytes in remission group before chemotherapy were lower than those in non-remission group(P<0.01); after chemotherapy, the expression levels of TF and VEGF on CD14~+ monocytes in remission group were lower than those before chemotherapy(P<0.05), while the TF and VEGF expression levels in non-remission group were no singnificauly different from TF and VEGF levels before chemtherapy(P>0.05), the survival of patients in group with low expression of TF and VEGF was superior to that in group with high expression of TF and VEGF(P<0.05). Conclusion: The paripheral blood CD14~+ monocytes in DLBCL patients highly express the TF and VEGF, which relate with IPI, therapeutic efficacy and survival, thus the TF and VEGF expression levels are of reference significance for evaluating the therapeutic efficacy and prognosis of patients.
Objective: To investigate the clinical significance of tissue factor(TF) and vascular endothelial growth factor(VEGF) expression on peripheral blood CD14 positive monocytes in patients with diffuse large B cell lymphoma(DLBCL). Methods: The expressions of TF and VEGF on peripheral CD14~+ monocytes in 41 patients with DLBCL(DLBCL group) before chemotherapy and after 4 chemotherapeutic courses, and in 20 healthy subjects(control group) were detected by flow cytometry respectively, meanwhile, the relationship of the expression of TF and VEGF with international prognostic indexes(IPI) and short-term effects were analysed. Results: The expression levels of TF and VEGF on peripheral CD14~+ monocytes in DLBCL group were significantly higher than those in control group(P<0.01), and a positive correlation was found between the two groups(r=0.755, P<0.01). The expression of TF and VEGF on CD14~+ monocytes in patients with prognostic risk factors significantly increased as compared with those in patients without prognostic risk factors(P<0.05), but there were no significant differences of TF and VEGF expressions on CD14~+ monocytes in DLBCL group with different sex, age, subtypes(P>0.05). As compared with patients without prognostic risk factors, the expression levels of TF and VEGF on CD14~+ monocytes of patients with prognostic risk factors significantly increased(P<0.05). The expression of TF and VEGF on CD14~+ monocytes in DLBCL group showed an increasing tendency along with the increase of IPI index(P<0.01). The expression levels of TF and VEGF on CD14~+ monocytes in remission group before chemotherapy were lower than those in non-remission group(P<0.01); after chemotherapy, the expression levels of TF and VEGF on CD14~+ monocytes in remission group were lower than those before chemotherapy(P<0.05), while the TF and VEGF expression levels in non-remission group were no singnificauly different from TF and VEGF levels before chemtherapy(P>0.05), the survival of patients in group with low expression of TF and VEGF was superior to that in group with high expression of TF and VEGF(P<0.05). Conclusion: The paripheral blood CD14~+ monocytes in DLBCL patients highly express the TF and VEGF, which relate with IPI, therapeutic efficacy and survival, thus the TF and VEGF expression levels are of reference significance for evaluating the therapeutic efficacy and prognosis of patients.
引文
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2 Biccler J,Eloranta S,de Nully Brown P,et al.Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma:a critical assessment of the R-IPI,IPI,and NCCN-IPI.Cancer Med,2018;7(1):114-122.
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5 Chen K,Li Z,Jiang P,et al.Co-expression of CD133,CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.J Cancer Res Clin Oncol,2014;32(2):755-763.
6 Lo L,Valentine H,Harrison J,et al.Tissue factor expression in the metaplasia-adenoma-carcinoma sequence of gastric cancer in a European population.Br J Cancer,2012;107(7):1125-1130.
7 Sui L,Liu K,Shen W,et al.Relationships between VEGF protein expression and pathological characteristics of diffuse large B cell lymphoma:a meta-analysis.Tumour Biol,2014;35(9):9085-9093.
8郭青,王加菊,李芳,等.VEGF和CXCR4在弥漫大B细胞淋巴瘤中的表达及其临床意义.中国实验血液学杂志,2013;21(2):383-386.
9 Deng C,Wu S,Zhang L,et al.Role of monocyte tissue factor on patients with non-small cell lung cancer.Clin Respir J,2018;12(3):1125-1133.
10 Cuadrado MJ,Buendía P,Velasco F,et al.Vascular endothelial growth factor expression in monocytes from patients with primary antiphospholipid syndrome.J Thromb Haemost,2006;4(11):2461-2469.
11 Chen Y,Neelapu S,Feng L,et al.Prognostic significance of baseline peripheral absolute neutrophil,monocyte and serumβ2-microglobulin level in patients with diffuse large b-cell lymphoma:a new prognostic model.Br J Haematol,2016;175(2):290-299.
12 Nitta H,Terui Y,Yokoyama M,et al.Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma.Haematologica,2015;100(1):87-90.
13 Katoh D,Ochi Y,Yabushita T,et al.Peripheral blood lymphocyteto-monocyte ratio at relapse predicts outcome for patients with relapsed or refractory diffuse large B-cell lymphoma in the rituximab era.Clin Lymphoma Myeloma Leuk,2017;17(12):e91-e97.
14徐玉秀,张勇刚,许春玲,等.淋巴细胞单核细胞比值对原发胃肠弥漫大B细胞淋巴瘤患者的临床特征和预后影响.中国实验血液学杂志,2016,24(5):1404-1409.
15 Harter PN,Dützmann S,Drott U,et al.Anti-tissue factor(TF9-10H10)treatment reduces tumor cell invasiveness in a novel migratory glioma model.Neuropathology,2013;33(5):515-25.
16 Li S,Tian Y,Zhao Y,et al.pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth.Oncotarget,2015;6(27):23523-23532.
2 Biccler J,Eloranta S,de Nully Brown P,et al.Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma:a critical assessment of the R-IPI,IPI,and NCCN-IPI.Cancer Med,2018;7(1):114-122.
3 Cheson BD,Horning SJ,Coiffier B,et al.Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas.NCI Sponsored International Working Group.J Clin Oncol,1999;17(4):1244.
4 Hahn N,Heiden M,Seitz R,et al.Inducible expression of tissue factor in small-cell lung cancer:impact on morphology and matrix metalloproteinase secretion.J Cancer Res Clin Oncol,2012;138(4):695-703.
5 Chen K,Li Z,Jiang P,et al.Co-expression of CD133,CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.J Cancer Res Clin Oncol,2014;32(2):755-763.
6 Lo L,Valentine H,Harrison J,et al.Tissue factor expression in the metaplasia-adenoma-carcinoma sequence of gastric cancer in a European population.Br J Cancer,2012;107(7):1125-1130.
7 Sui L,Liu K,Shen W,et al.Relationships between VEGF protein expression and pathological characteristics of diffuse large B cell lymphoma:a meta-analysis.Tumour Biol,2014;35(9):9085-9093.
8郭青,王加菊,李芳,等.VEGF和CXCR4在弥漫大B细胞淋巴瘤中的表达及其临床意义.中国实验血液学杂志,2013;21(2):383-386.
9 Deng C,Wu S,Zhang L,et al.Role of monocyte tissue factor on patients with non-small cell lung cancer.Clin Respir J,2018;12(3):1125-1133.
10 Cuadrado MJ,Buendía P,Velasco F,et al.Vascular endothelial growth factor expression in monocytes from patients with primary antiphospholipid syndrome.J Thromb Haemost,2006;4(11):2461-2469.
11 Chen Y,Neelapu S,Feng L,et al.Prognostic significance of baseline peripheral absolute neutrophil,monocyte and serumβ2-microglobulin level in patients with diffuse large b-cell lymphoma:a new prognostic model.Br J Haematol,2016;175(2):290-299.
12 Nitta H,Terui Y,Yokoyama M,et al.Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma.Haematologica,2015;100(1):87-90.
13 Katoh D,Ochi Y,Yabushita T,et al.Peripheral blood lymphocyteto-monocyte ratio at relapse predicts outcome for patients with relapsed or refractory diffuse large B-cell lymphoma in the rituximab era.Clin Lymphoma Myeloma Leuk,2017;17(12):e91-e97.
14徐玉秀,张勇刚,许春玲,等.淋巴细胞单核细胞比值对原发胃肠弥漫大B细胞淋巴瘤患者的临床特征和预后影响.中国实验血液学杂志,2016,24(5):1404-1409.
15 Harter PN,Dützmann S,Drott U,et al.Anti-tissue factor(TF9-10H10)treatment reduces tumor cell invasiveness in a novel migratory glioma model.Neuropathology,2013;33(5):515-25.
16 Li S,Tian Y,Zhao Y,et al.pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth.Oncotarget,2015;6(27):23523-23532.