趋化性细胞因子与乳腺癌的转移

远处转移是乳腺癌致死和预后较差的重要原因，而在乳腺癌转移中，趋化性细胞因子扮演着重要角色，乳腺癌细胞高表达某些趋化性细胞因子及某些受体，通过趋化性细胞因子与其受体的相互作用，趋化吞噬细胞及淋巴细胞浸润，促使癌细胞侵入正常组织及血管生成，形成转移肿瘤。本文主要综述了近年研究较多的趋化性细胞因子受体CXCR4及趋化性细胞因子RANTES、IL-8、MCP-1等在乳腺癌转移中的作用。     

乳腺癌组织中IL-8和MVD的表达与预后关系

目的：检测乳腺癌组织中IL-8和微血管密度（microvessel density,MVD）表达,探讨其与临床病理学因子及生物学因子的关系.方法：采用免疫组化SP法检测乳腺癌组织中IL-8、ER、PR、VEGF和CD105的表达.结果：1）103例乳腺癌组织中,IL-8阳性表达率为79.6%（82/103）,正常及良性组织IL-8阳性率为13.8%（4/29）,两者相比差异有统计学意义,P=0.000.2）MVD计数值范围为0～17.67,中位数为5.33.3）IL-8与VEGF和MVD表达均呈现正相关性,rs值分别为0.332和0.425,P值均为0.000.4）IL-8与淋巴结转移及临床分期有关,P值分别为0.002和0.024.5）IL-8与ER、PR、肿瘤大小及病理类型无关,P值分别为0.449、0.467、0.921和0.145.6）IL-8表达和MVD与乳腺癌预后有关,P值分别为0.006和0.002.结论：IL-8表达和MVD与影响乳腺癌患者预后的生物学因素相关,IL8和MVD高表达,预后差,可作为判断乳腺癌预后指标.     

血清IL-1β、IL-10、MCP-1水平变化对霍奇金淋巴瘤患者早期诊断和疗效预测的价值

目的:观察血清IL-1β、IL-10、MCP-1水平变化对霍奇金淋巴瘤患者早期诊断和疗效预测的价值。方法:选取2015年1月至2018月12月我科收治的霍奇金淋巴瘤患者82例（实验组），健康志愿者60例（对照组），检测两组血清IL-1β、IL-10、MCP-1的表达情况，比较霍奇金淋巴瘤在不同分期中的血清IL-1β、IL-10、MCP-1表达水平，分析血清IL-1β、IL-10、MCP-1对霍奇金淋巴瘤早期诊断和疗效预测的价值。结果:实验组患者治疗前血清IL-1β、IL-10、MCP-1水平分别高于对照组血清IL-1β、IL-10、MCP-1水平（P<0.05）。霍奇金淋巴瘤患者Ⅳ期血清IL-1β、IL-10、MCP-1水平分别高于Ⅰ、Ⅱ、Ⅲ期患者血清IL-1β、IL-10、MCP-1水平（P<0.05）。实验组患者治疗后血清IL-1β、IL-10、MCP-1水平分别低于实验组患者治疗前血清IL-1β、IL-10、MCP-1水平（P<0.05）。ROC曲线示:血清IL-1β、IL-10、MCP-1曲线下面积分别为0.788、0.800、0.696，敏感度分别为0.771、0.825、0.743，特异度分别为0.688、0.750、0.625。联合测定曲线下面积为0.906，敏感度和特异度分别为0.886和0.875。结论:血清IL-1β、IL-10、MCP-1在霍奇金淋巴瘤患者中呈现异常高表达，血清IL-1β、IL-10、MCP-1可能参与霍奇金淋巴瘤的发生发展，可作为霍奇金淋巴瘤诊断的预测指标之一。     

CD44v6蛋白在乳腺癌中的表达及其预后意义

目的；研究CD44v6蛋白在乳腺癌中的表达，并探讨其能否成为乳腺癌的预后影响因素。方法：应用EnVision^TM免疫组化法，回顾性分析100例女性浸润性导管癌石蜡组织CD44v6的表达。结果：CD44v6在乳腺癌中表达的阳性率为66％。CD44v6的表达与患者淋巴结转移状况、临床分期密切相关。Kaplan-Meier生存曲线，Logrank检验结果显示，CD44v6低表达患者的五年、十年生存率分别为82．76％，78．37％。而CD44v6高表达的患者的五年、十年生存率分别为64．1％、49．88％，两者之间存在显著性差异（P＝0．0055）。结论：CD44v6蛋白与乳腺癌淋巴结转移相关，可能作为有意义的预后指标指导临床。     

乳腺癌组织中IL-8和MVD的表达与预后关系

目的:检测乳腺癌组织中IL-8和微血管密度(microvessel density,MVD)表达,探讨其与临床病理学因子及生物学因子的关系。方法:采用免疫组化SP法检测乳腺癌组织中IL-8、ER、PR、VEGF和CD105的表达。结果:1)103例乳腺癌组织中,IL-8阳性表达率为79.6%(82/103),正常及良性组织IL-8阳性率为13.8%(4/29),两者相比差异有统计学意义,P=0.000。2)MVD计数值范围为0~17.67,中位数为5.33。3)IL-8与VEGF和MVD表达均呈现正相关性,rs值分别为0.332和0.425,P值均为0.000。4)IL-8与淋巴结转移及临床分期有关,P值分别为0.002和0.024。5)IL-8与ER、PR、肿瘤大小及病理类型无关,P值分别为0.449、0.467、0.921和0.145。6)IL-8表达和MVD与乳腺癌预后有关,P值分别为0.006和0.002。结论:IL-8表达和MVD与影响乳腺癌患者预后的生物学因素相关,IL-8和MVD高表达,预后差,可作为判断乳腺癌预后指标。     

乳腺癌VEGF的表达与肿瘤生物学特性的关系

目的：研究血管内皮生长因子（VEGF）在乳腺癌组织中的表达及其与临床生物学特性的关系。方法：应用免疫组化S-P法和RT-PCR法检测VEGF、在42例乳腺癌和相应正常乳腺组织中的表达。结果：免疫组化和RT-PCR检测结果显示，42例乳腺癌组织中VEGF的阳性表达率分别为59，5％（25／42）和73．8％（31／42），明显高于正常乳腺组织VEGF的阳性率16．7％（7／42）和23，8％（10／42），VEGF的高表达与乳腺癌患者淋巴结转移密切相关。结论：乳腺癌组织中存在VEGF的过量表达，并且与癌组织淋巴结转移有关：检测VEGF有可能作为预测乳腺癌转移潜能和预后的重要指标。     

乳腺癌新辅助化疗前后外周血中微转移癌细胞的变化及其临床意义的研究

目的：观察乳腺癌患者新辅助化疗前后外周血微转移的变化，并探讨其临床意义。方法：44例乳腺癌患者首先经半定量逆转录聚合酶链反应（RT-PCR）检测外周血CK-20 mRNA为阳性表达，给予CEF方案行新辅助化疗后，再次检测外周血CK-20 mRNA的表达，并评价化疗对肿瘤的疗效。结果：新辅助化疗后14例（31．8％）乳腺癌患者外周血CK-20 mRNA表达转为阴性，21例（47．7％）表达下降，9例（20．5％）未见明显变化，与化疗前相比差异有统计学意义，P=0．006；化疗疗效临床完全缓解3例（6．8％），部分缓解34例（77．3％），疾病稳定7例（15．9％），无疾病进展病例；CK-20表达下降与新辅助化疗疗效显著相关，r=0．942。结论：新辅助化疗可明显降低乳腺癌患者外周血微转移的发生，并可作为化疗疗效判定的早期预测指标。     

MUC1和CK7在乳腺癌外周血微转移检测中的应用

目的：以MUC1和CK7为基因标志物检测乳腺癌患者外周血中播散的肿瘤细胞，探讨肿瘤基因标志物在乳腺癌微转移诊断中的意义。方法：采用RT—PCR法检测乳腺癌患者外周血中有核细胞的MUC1和CK7mRNA表达。结果：1）检测15例正常人外周血MUC1、CK7mRNA表达，结果无假阳性；将乳腺癌细胞系MCF-7分别以1：10^5、1：10^6与正常外周血有核细胞混合，检测MUC1、CK7表达，结果无假阴性。2）检测35例乳腺癌患者外周血，以MUC1为标志物，外周血中肿瘤细胞检出率为30_3％（11／35）；以CK7为标志物，外周血中肿瘤细胞检出率为35．0％（12／35）。3）35例患者中有4例MUC1、CK7均表达阳性，7例仅MUC1表达阳性，8例仅CK7表达阳性，两种肿瘤标志物表达患者有交叉但不重叠。结论：以MUC1、CK7为基因标志物，采用RT—PCR方法检测乳腺癌患者外周血中的肿瘤细胞可能在乳腺癌微转移诊断及乳腺癌预后中具有意义，多种肿瘤基因标志物联合检测结果优于单一标志物检测。     

乳腺癌组织CXCR4和HIF-1α表达及其临床意义的研究

目的：探讨趋化因子受体CXCR4和HIF-1α与乳腺癌淋巴结转移的关系。方法：选择48例乳腺癌标本，应用免疫组织化学染色法检测CXCR4和HIF-1α在人乳腺癌组织中的表达，同时对其与临床病理参数的关系进行统计学分析。结果：CXCR4在乳腺癌组织中的阳性表达率为52.1％，其中淋巴结转移组表达率为75．0％，无淋巴结转移组表达率为40．6％，差异有统计学意义，P=0．025。HIF-1α在乳腺癌组织中的阳性表达率为50．0％，其中淋巴结转移组表达率为75．0％，无淋巴结转移组表达率为37．5％，差异有统计学意义，P=0.014。CXCR4阳性表达与HIF-1α阳性表达呈显著正相关，P=0．001。乳腺癌CXCR4和HIF-1α的表达水平与肿瘤细胞淋巴结转移密切相关，而与患者的年龄、肿瘤大小和组织学类型等无相关性。结论：乳腺癌组织中有CX-CR4及HIF-1α的表达，其表达水平与乳腺癌淋巴结转移相关。     

胃肠道癌患者外周血癌胚抗原信使核糖核酸的检测及其临床意义

目的：应用RT—PCR法检测胃肠道癌患者外周静脉血CEAmRNA，探讨与不同临床病理指标之间的关系，评估对临床治疗和预后的指导意义。方法：应用RT—PCR技术，选择特异性CEAmRNA引物，检测41例胃癌、大肠癌患者外周血CEAmRNA，同时定量检测外周血CEA和CA19—9糖蛋白。另抽取12例健康志愿者外周血标本作为对照。结果：41例胃肠癌患者外周血中CEAmRNA、CEA、CA19—9阳性率分别为26．8％、19．5％、14．6％。12例对照外周血中CEAmRNA、CEA、CA19—9均阴性。有淋巴结转移者外周血CEAmRNA阳性率（40％，10／25）高于无淋巴结转移者（6．25％，1／16），P=0．000。TNM分期Ⅳ期中外周血CEAmRNA阳性率63．6％（7／11），Ⅲ期21．4％（3／14），Ⅰ、Ⅱ期6．3％（1／16），P=0．004。外周血CEAmRNA表达在不同年龄、性别、病理类型中无统计学差异（P〉0．05）。结论：CEAmRNA、CEA和CA19—9在胃肠道癌患者中的阳性率，以CEAmRNA阳性率最高，随淋巴结转移数目、病期进展，阳性率更高，可能预后不良。     

Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology

We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre- and post-vaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)-1alpha, -1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -15, -17, IFN-gamma, G-CSF, GM-CSF, TNF-alpha, IP-10, MIP-1alpha, RANTES, eotaxin and monocyte chemotactic protein-1 (MCP-1) were assessed. Six of 22 cytokines showed significant differences between BCa and healthy controls. MCP-1, eotaxin, RANTES and GM-CSF levels were significantly elevated in BCa (P<0.009) and IL-1alpha and IL-4 levels were significantly decreased in BCa (P<0.015). Cytokine levels were generally elevated in NN patients compared to NP patients with the exception of eotaxin and IL-13, which were increased in NP patients. Three cytokines, IL-6, MIP-1alpha and G-CSF reached statistical significance (P<0.05). In 34 vaccinated BCa, MCP-1, eotaxin and IL-13 were significantly elevated post-vaccination with MCP-1 demonstrating the most significant response (median, 145.8-217.0 pg/ml, P=0.003). Using a multiplex assay we found significant differences in cytokine levels in sera of BCa compared to healthy controls, in NN compared to NP patients, and in vaccinated patients. Our results support an extended analysis of serum cytokine profiles for the potential development of predictive panels in diagnosis, staging and monitoring cancer vaccine trials.     

Elevated levels of circulating platelet microparticles,VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor

The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles (PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (n=109) and in healthy controls (n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.     

Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma

Background:

Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis.

Methods:

The serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil–lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls.

Results:

CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls – including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) – yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu.

Conclusion:

CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.     

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

It has been hypothesized that inflammatory response triggered by surgery might induce the release of molecules that could promote proliferation, invasion and metastasis of surviving cancer cells. To test this hypothesis, the levels of multiple inflammation-related circulating factors were analyzed in patients undergoing surgery for colorectal cancer. A Luminex xMAP system was used to simultaneously assess levels of IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α and VEGF in 20 colorectal cancer patients and 10 age-matched non-neoplastic patients. In cancer patients analyses were performed at baseline (before surgery) and at different time points (up to 30 days) following laparoscopic surgery. Significantly higher levels of IL-1β, IL-7, IL-8, G-CSF, IFN-γ and TNF-α were detected in colorectal cancer patients compared to controls at baseline. In colorectal cancer patients, circulating levels decreased progressively following surgery and after day 30 post-surgery were no longer different from controls. These findings suggest that expression levels of several cytokines are higher in colorectal cancer patients compared to control subjects and no significant increase in several inflammation-related circulating factors is observed following laparoscopic surgery for cancer. Confirmation and validation in a different and larger cohort of patients are warranted.     

Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival.

PURPOSE: The prognostic significance of serum interleukin (IL)-8 was evaluated in patients with metastatic breast cancer. The predictive value of serum IL-8 for the presence of occult metastatic tumor cells in bone marrow aspirates was evaluated in patients with operable and metastatic breast cancer. EXPERIMENTAL DESIGN: Serum IL-8 was measured in healthy controls, patients with operable breast cancer, and patients with untreated, progressive metastatic breast cancer. In 69 patients with either operable or advanced breast cancer, occult cytokeratin-positive cells were counted in bone marrow aspirates. RESULTS: Serum IL-8 levels are increased in 67% (52 of 77) of patients with advanced breast cancer. Overall, these levels are significantly higher in patients with breast cancer compared with healthy volunteers (P < 0.001). The IL-8 levels increase significantly in patients with more advanced disease. An elevated serum IL-8 is related to an accelerated clinical course, a higher tumor load, and the presence of liver or lymph node involvement. A multivariate analysis indicates that serum IL-8 is an independent significant factor for postrelapse survival. There was a significant difference between serum IL-8 levels in patients with or without occult cytokeratin-positive bone marrow cells (P < 0.04). Serum IL-8 levels also showed an association with the number of these cells (P < 0.01). CONCLUSIONS: Serum IL-8 is increased in patients with breast cancer and has an independent prognostic significance for postrelapse survival. The observations on the relationship between occult cytokeratin-positive bone marrow cells corroborate the concept of IL-8 acting as a contributor to the process of tumor cell dissemination. Similarly, the relationship between serum IL-8 and nodal stage at presentation deserves further study. These results further expand the concept that inflammation and inflammatory cytokines are critical components of tumor progression.     

Effects of thymic peptides, in vitro, on the impaired immunocytotoxicity of peripheral blood mononuclear cells from tumor patients

The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural killer (NK) cell activities than colorectal tumor patients and normal controls. In contrast, the generation of lymphokine (IL-2) activated killer (LAK) cells was found to be comparable within the different tumor diseases (24% cytotoxicity), but lower than in the group of normal controls. TP, being without any effects on NK cell activity in all groups, increased the deficient LAK cell activity of breast tumor and melanoma patients, as well as of normal controls? without significant effects on PBL from colorectal tumor patients. This increase was found to be associated with an increase of the IL-2 induced IFN-gamma and, on a lower level, TNF-alpha secretion, especially from breast tumor and melanoma patients. In addition, monocytes from these patients showed a deranged tumoristatic activity, compared to colorectal tumor patients and normal controls. The stimulation of monocytes by IFN-gamma greatly elevated the mean of the antitumor activity in all groups studied. TP being slightly effective on monocytes from melanoma patients, did not further enhance monocyte-mediated cytotoxicity when applied alone or in combination with IFN-gamma. Reduced basal monocytic chemokine levels were only found in the groups of melanoma (IL-8) and colorectal tumor patients (MCP-1), whereas RANTES secretion was increased, compared to normal controls. TP was active only in reducing the IL-8 secretion of monocytes from colon tumor patients. The results indicate that selected functions of peripheral blood mononuclear cells can be partially improved by the thymic peptide preparation.     

Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b.

PURPOSE: Interferon (IFN)-alpha2b is the only Food and Drug Administration-approved treatment for operable high-risk melanoma that has been shown to significantly and durably prolong relapse-free survival (RFS) of patients with stage IIB-III melanoma. Development of reliable serum assays may contribute to the development of methods for earlier detection of melanoma and the selection of patients who may be most susceptible to current available interventions with IFNalpha. EXPERIMENTAL DESIGN: A powerful high-throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) was used to simultaneously test 29 cytokines, chemokines, angiogenic as well as growth factors, and soluble receptors in the sera of 179 patients with high-risk melanoma and 378 healthy individuals. RESULTS: Serum concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, IL-12p40, IL-13, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, IFNalpha, tumor necrosis factor (TNF)-alpha, epidermal growth factor, vascular endothelial growth factor (VEGF), and TNF receptor II were found to be significantly higher in patients with resected high-risk melanoma compared with healthy controls. Bayesian Network algorithm classification of the data offered 90% sensitivity at 98% specificity with 96.5% of melanoma patients distinguished from healthy individuals. IFN-alpha2b therapy resulted in a significant decrease of serum levels of immunosuppressive and tumor angiogenic/growth stimulatory factors (VEGF, epidermal growth factor, and hepatocyte growth factor) and increased levels of antiangiogenic IFN-gamma inducible protein 10 (IP-10) and IFN-alpha. Pretreatment levels of proinflammatory cytokines IL-1beta, IL-1alpha, IL-6, TNF-alpha, and chemokines MIP-1alpha and MIP-1beta were found to be significantly higher in the serum of patients with longer RFS values of 1 to 5 and >5 years when compared with patients with shorter RFS of <1 year. CONCLUSION: These data show that multiplexed analysis of serum biomarkers is useful for the evaluation of prognostic markers of clinical outcome and potential predictive markers of response to IFN-alpha2b in patients with high-risk operable melanoma.     

Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer.

The beta-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I. A marked increase in plasma RANTES level (> 10,000 pg/ml) was found in 27% of patients with progressive malignancy but in none of those in clinical remission. The platelet RANTES content was correspondingly decreased in those patients with increased plasma RANTES levels. Beta-TG showed a pattern similar to RANTES both in plasma and platelets, but with much less dramatic differences between patients with different stages of disease. Other allergic parameters, IgE, eosinophils and plasma IFN-gamma, IL-2, -5, and -10, were not elevated in the cancer patients. The RANTES content was markedly elevated in the primary tumor and metastatic lesions (lymph node or skin) from all of the patients with breast or cervical cancer, irrespective of the plasma RANTES level. In addition, in patients with progressive breast or cervical cancer, but not in patients thought to be cured of these tumors, the RANTES content was markedly increased in clinically normal tissue taken from near the operative site several months postoperatively, as well as in intact skin or mucosa taken perioperatively near the excised tumor. This study suggests an as-yet-undefined but important role played by RANTES in carcinogenesis, as well as the possibility that a RANTES assay in tissue surrounding a tumor or postoperative tumor site may help predict prognosis in these patients.     

结直肠癌患者术前焦虑状态与细胞因子水平变化关系的研究

目的:探究结直肠癌（colorectal cancer,CRC）患者术前焦虑状态与血浆细胞因子水平变化的关系。方法:选取结直肠癌患者93名,采用汉密尔顿焦虑量表（Hamilton Rating Scale for Anxiety,HAMA）、纽芬兰纪念大学主观幸福感量表（Memorial University of Newfoundland Scale of Happiness,MUNSH）、癌症患者生命质量测定量表（Quality of Life Questionnaire,QLQ-C30）、自尊量表（self-esteem scale,SES）评估患者身心健康状况,根据HAMA评分将CRC患者分为三组:HAMA<7（无焦虑组）42人,7≤HAMA＜14(可能焦虑组)30人,HAMA≥14(焦虑组)21人。用LUMINEX（悬液芯片技术）检测各组血浆G-CSF、GM-CSF、IL-2、IL-6、IL-8、IL-10、IL-12p70、IL-13、IL-17A、IL-1β、MCP-1、TNF-α、IFN-γ水平。结果:无焦虑组和可能焦虑组、焦虑组的MUNSH、SES、QLQ-C30总分的差异均有统计学意义（P<0.05）,可能焦虑组和焦虑组MUNSH、SES、QLQ-C30总分的差异无统计学意义（P>0.05）。三组CRC患者的G-CSF、GM-CSF、IL-2、IL-6、IL-8、IL-10、IL-12p70、IL-1β、MCP-1、TNF-α、IFN-γ随HAMA分值的增高存在相似的倒“V”型变化趋势:细胞因子在HAMA＜7组水平最低,在7≤HAMA＜14组水平最高,在HAMA＞14组较前者出现下降,但仍高于HAMA＜7组（IL-1β除外）。G-CSF（P=0.017、IL-10(P=0.035)、IL-12p70(P=0.047)、IFN-γ(P=0.029)在三组之间的差异有统计学意义。结论:不同焦虑程度的结直肠癌患者外周血中的细胞因子水平有所不同,可能焦虑组的结直肠癌患者同样需要临床和科研工作者的重视。     

Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7.

PURPOSE: To evaluate if serum cytokine levels could be used as diagnostic or prognostic markers in ovarian cancer. EXPERIMENTAL DESIGN: A cytokine bead array was done to simultaneously analyze 14 cytokines in the sera of 187 ovarian cancer patients with complete clinicopathologic data and follow-up, 45 patients with benign ovarian tumors, and 50 healthy controls. Serum levels of the well-known serum tumor marker CA-125 were routinely measured in all patients. RESULTS: Serum levels of CA-125, interleukin 6 (IL-6), IL-7, and IL-10 were elevated in ovarian cancer patients compared with patients with benign ovarian tumors. Analyzing the cytokines in combination with CA-125 showed that a combination of IL-7 and CA-125 serum levels could accurately predict 69% of the ovarian cancer patients, without falsely classifying patients with benign pelvic mass. The cytokines IL-6, IL-7, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), and IP-10 and CA-125 were associated with disease-free and overall survival in univariate analysis. In multivariate analysis, IL-7 and IP-10 were independent predictors of overall survival, although after inclusion of the clinicopathologic parameters, only stage and residual disease remained as independent predictors of survival. CONCLUSIONS: IL-7 levels were found to be strongly associated with ovarian cancer and could be used in combination with CA-125 to distinguish between malignant and benign ovarian tumors.