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Admasu FT, Dejenie TA, Ayehu GW, Zewde EA, Dessie G, Adugna DG, Enyew EF, Geto Z, Abebe EC. Evaluation of thromboembolic event, basic coagulation parameters, and associated factors in patients with colorectal cancer: a multicenter study. Front Oncol 2023; 13:1143122. [PMID: 37205202 PMCID: PMC10188115 DOI: 10.3389/fonc.2023.1143122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/13/2023] [Accepted: 04/14/2023] [Indexed: 05/21/2023] Open
Abstract
Background Patients with colorectal cancer are at an increased risk of hemostatic disturbances, and recent studies have shown that coagulation disorders could be the first sign of malignancy. Although coagulopathy is a significant cause of cancer-related death and disability, it is usually underestimated, and there has been no recent scientific evidence regarding the exact burden and its specific determinants. Moreover, the public health importance of the risk of coagulopathy among patients with colorectal polyps has not been addressed. Materials and methods An institution-based comparative cross-sectional study was conducted on a total of 500 study participants (250 colorectal cancer patients, 150 colorectal polyp patients, and 100 controls) from January to December 2022. Venous blood was collected for basic coagulation and platelet analysis. Descriptive statistics and non-parametric tests (Kruskal-Wallis and Dunn-Bonferroni pairwise comparisons) were used to compare study parameters among the groups. The test results were expressed as medians and interquartile ranges. Binary logistic regressions were fitted, and statistical significance was declared at a p-value of less than 0.05, with 95% CI. Results The prevalence of coagulopathy among colorectal cancer patients was 198 (79.2%; 95% CI: 73.86, 83.64), while the prevalence was 76 (50.7%; 95% CI: 45.66, 54.34) among colorectal polyp patients. From the final model, age between 61 and 70 (AOR = 3.13: 95% CI: 1.03, 6.94), age > 70 years (AOR = 2.73: 95% CI: 1.08, 4.71), hypertension (AOR = 6.8: 95% CI: 1.07, 14.1), larger tumor size (AOR = 3.31: 95% CI: 1.11, 6.74), metastatic cancer (AOR = 5.8: 95% CI: 1.1, 14.7), and BMI ≥30 kg/m2 (AOR = 3.8: 95% CI: 2.3, 4.8) were positively associated with coagulopathy. Conclusion This study showed that coagulopathy is a major public health concern among patients with colorectal cancer. Therefore, existing oncology care efforts should be strengthened to prevent coagulopathy among patients with colorectal cancer. Moreover, patients with colorectal polyps should receive more attention.
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Affiliation(s)
- Fitalew Tadele Admasu
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
- *Correspondence: Fitalew Tadele Admasu,
| | - Tadesse Asmamaw Dejenie
- Department of Biochemistry, School of Medicine, College of Health Sciences and Medicine, Gondar University, Gondar, Ethiopia
| | - Gashaw Walle Ayehu
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Edget Abebe Zewde
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Gashaw Dessie
- Department of Biochemistry, School of Medicine, College of Health Sciences and Medicine, Gondar University, Gondar, Ethiopia
| | - Dagnew Getnet Adugna
- Department of Anatomy, School of Medicine, College of Medicine and Health Science, Gondar University, Gondar, Ethiopia
| | - Engidaw Fentahun Enyew
- Department of Anatomy, School of Medicine, College of Medicine and Health Science, Gondar University, Gondar, Ethiopia
| | - Zeleke Geto
- Department of Biomedical Sciences, School of Medicine, College of Health Sciences, Wello University, Wello, Ethiopia
| | - Endeshaw Chekol Abebe
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
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Liu B, Li B, Zhou P, Yue W, Wang T, Wang J, Hu X, Zhang W, Chen J, Chen L, Gao L, He M, Yang J. Prognostic value of pretreatment plasma D-dimer levels in patients with diffuse large B cell lymphoma (DLBCL). Clin Chim Acta 2018; 482:191-198. [PMID: 29649456 DOI: 10.1016/j.cca.2018.04.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/04/2018] [Revised: 04/06/2018] [Accepted: 04/08/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND We assessed the prognostic significance of D-dimer in patients of diffuse large B cell lymphoma (DLBCL). METHODS We performed a retrospective study including 254 patients who were newly diagnosed DLBCL. X-tile was used to generate a cutoff value for D-dimer. Both univariate screen by Cox proportional hazard model and multivariable analysis by Cox regression model were used to assess the impact of pretreatment D-dimer levels on the overall survival (OS). RESULT According to X-tile, the optimal cut-off value of D-dimer for prediction of survival was set as 1.6 μg/mL, and a D-dimer level ≥ 1.6 μg/mL was significantly associated with poor overall survival (OS) (OS: 31.7 vs. 79.1%, P < 0.001). In multivariable analysis, it was found that a higher D-dimer level was an independent predictor for worse OS (Hazard ratio (HR): 3.594 95% Confidence interval (CI): 2.296-5.267, P < 0.001). In subgroup analysis of International Prognostic Index (IPI), survival of low-risk and intermediate-risk group with a D-dimer level ≥ 1.6 μg/mL were both similar to that of the high-risk group (OS: 31.6 vs. 36.5%, P = 0.957; OS: 38.0 vs. 36.5%, P = 0.758). In addition, among patients treated with surgery, those with higher D-dimer had substantially worse survival than that with lower D-dimer (OS: 27.0 vs. 84.5%, P < 0.001). CONCLUSION Pretreatment D-dimer is a simple but effective predictor of survival among patients with DLBCL.
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Affiliation(s)
- Bin Liu
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Bo Li
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Pingting Zhou
- Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenqin Yue
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Tao Wang
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Jianmin Wang
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Xiaoxia Hu
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Weiping Zhang
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Jie Chen
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Li Chen
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Lei Gao
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
| | - Miaoxia He
- Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
| | - Jianmin Yang
- Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
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Uccella S, Cromi A, Vigetti D, Cimetti L, Deleonibus S, Casarin J, Passi A, Riva C, Ghezzi F. Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis. J OBSTET GYNAECOL 2015; 36:353-8. [DOI: 10.3109/01443615.2015.1065231] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/20/2023]
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Li Y, Wei S, Wang J, Hong L, Cui L, Wang C. [Analysis of the factors associated with abnormal coagulation and prognosis
in patients with non-small cell lung cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2015; 17:789-96. [PMID: 25404269 PMCID: PMC6000357 DOI: 10.3779/j.issn.1009-3419.2014.11.04] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Indexed: 01/01/2023]
Abstract
背景与目的 凝血及纤溶系统激活在肺癌患者中较为常见,与肺癌侵袭、转移的高风险和预后差相关。非小细胞肺癌(non-small cell lung cancer, NSCLC)占肺癌的80%-85%,本研究旨在回顾性分析凝血功能指标对NSCLC的预后价值,为目前NSCLC患者高凝状态的预防及治疗提供参考。 方法 回顾性分析2009年1月-2012年12月首次就诊于河北医科大学第四医院的604例经病理学证实的NSCLC患者的临床资料。资料内容包括患者治疗前凝血功能相关指标[血浆凝血酶原时间(prothrombin time, PT)、凝血酶原活动度(prothrombin time activity, PTA)、国际标准化比率(international normalized ratio, INR)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、纤维蛋白原(fibrinogen, Fib)、D二聚体(D-dimer, D-D)、血小板计数(platelet count, PLT)]、性别、年龄、病理分型、TNM分期、淋巴结状态等。本研究选择了50例同期就诊于河北医科大学第四医院的非癌症患者作为对照组。采用SPSS 13.0统计软件进行分析。 结果 NSCLC组与对照组之间所有的凝血功能指标(包括PT、PTA、INR、APTT、Fib、D-D、血小板计数)的血浆水平显示均有统计学差异[除了Fib(P=0.001, 5)、Plt(P=0.004, 5),其余指标(P<0.001)]。纤维蛋白原水平与NSCLC的组织学亚型之间相关,鳞癌比腺癌的Fib水平明显升高(P<0.001)。Ⅲ期、Ⅳ期期比Ⅰ期-Ⅱ期患者的Fib、PLT水平升高(P<0.001, P=0.014),APTT缩短(P<0.001)。与N0患者相比,N1-N3患者的APTT,明显缩短(P<0.001),Fib、D-D水平升高(P<0.001, P=0.048)。对生存率的比较研究显示,PT、INR延长(P=0.032, P=0.001),Fib升高(P<0.001),PTA下降(P=0.005),在统计学上对总生存有明显的不利影响。多因素生存分析显示,在凝血功能指标中INR是唯一的独立预后因素(P=0.017)。 结论 NSCLC患者往往存在凝血纤溶系统的激活,导致凝血纤溶指标的亚临床改变。肺腺癌患者以及分期为晚期、淋巴结存在转移的NSCLC患者更易出现高血凝状态。PT、INR的延长与NSCLC患者生存率的下降密切相关,INR是NSCLC的独立预后因素,PT、INR可能成为NSCLC的预后指标。
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Affiliation(s)
- Yanhua Li
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Suju Wei
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Junyan Wang
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Lei Hong
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Lige Cui
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Cai Wang
- Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
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High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis. Tumour Biol 2013; 34:3701-4. [PMID: 23873105 DOI: 10.1007/s13277-013-0953-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/27/2013] [Accepted: 06/17/2013] [Indexed: 01/24/2023] Open
Abstract
An elevated plasma D-dimer level indicates the activation of coagulation and fibrinolysis. Several studies suggested that high level of plasma D-dimer was associated with the prognosis of lung cancer. In the present study, we performed a meta-analysis to evaluate the relationship between plasma D-dimer level and the prognosis of lung cancer based on larger sample size. We retrieved the literature, assessed and selected the data, and performed the statistical analysis according to the RevMan 5.0 guidelines. Literature-based searching was guided to gather data, and fixed-effects model was used to pool the hazard ratio according to the test of heterogeneity. A total of seven eligible studies including 1,377 lung cancer patients were analyzed. Survival time was significantly better in patients in the low D-dimer group than those in the high D-dimer group (hazard ratio for high D-dimer group = 1.12; 95% confidence interval 1.02 to 1.23). Patients with high levels of D-dimer have a poorer overall survival compared with those patients with low levels of D-dimer.
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Affiliation(s)
- L R Zacharski
- Department of Medicine, Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
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Ghezzi F, Cromi A, Siesto G, Giudici S, Serati M, Formenti G, Franchi M. Prognostic significance of preoperative plasma fibrinogen in endometrial cancer. Gynecol Oncol 2010; 119:309-13. [PMID: 20688365 DOI: 10.1016/j.ygyno.2010.07.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/16/2010] [Revised: 07/10/2010] [Accepted: 07/14/2010] [Indexed: 10/19/2022]
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Abstract
Tissue factor (TF), apart from its established role in hemostasis, has been implicated in promoting angiogenesis and metastasis in a wide array of tumors including prostate cancer. Expression of TF was evaluated in freshly-resected prostate specimens obtained from patients with localized (n=9) and androgen ablated (n=6) disease using real-time reverse transcription-polymerase chain reaction and Western blot analysis. TF was detected in all specimens in both stages of the disease. We further analyzed for correlations between TF expression and those of several angiogenic growth factors and their receptors. TF RNA expression correlated significantly with expression of vascular endothelial growth factor-A in these specimens (s=0.621, P=0.013). Eighty-one prostate specimens from patients with benign prostatic hyperplasia (n=27), localized prostate cancer (ES, n=32), and advanced disease (n=22) were also evaluated using immunohistochemistry and findings were correlated with clinical parameters. TF expression was detected on epithelial cells of the malignant glands. Furthermore, its expression levels correlated significantly with Gleason score (s=0.58, P=0.0001) and with the stage of the disease (s=0.441, P=0.0001) in these specimens. These data support the role of TF in angiogenesis and disease progression.
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Jones JM, McGonigle NC, McAnespie M, Cran GW, Graham AN. Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer. Lung Cancer 2006; 53:97-101. [PMID: 16698114 DOI: 10.1016/j.lungcan.2006.03.012] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/03/2005] [Revised: 03/07/2006] [Accepted: 03/13/2006] [Indexed: 12/11/2022]
Abstract
OBJECTIVES There is an association between coagulation and lung cancer. Therefore, pre-operative plasma fibrinogen and serum C-reactive protein (CRP) concentration were assessed to determine their association with tumour characteristics and to ascertain any role in patient selection for curative resection. METHODS These parameters were compared with tumour size, pTNM stage, and possibility of complete resection in 93 patients with non-small cell lung cancer who underwent surgical resection. RESULTS Plasma fibrinogen concentration (r(s)=0.34, P=0.001) and serum CRP concentration (r(s)=0.34, P=0.001) were positively correlated with maximum pathological tumour size. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.5+/-0.13 g/L versus 3.6+/-0.28 g/L; P=0.008), with a trend towards a similar association for CRP (P=0.06). Pathological T stage was also associated with mean plasma fibrinogen and serum CRP concentration (P=0.01 and 0.04, respectively), but pN stage was not associated with either parameter. Incomplete resection occurred in 23% of patients with plasma fibrinogen > 5 g/L or serum CRP > 40 mg/L (versus only 8% when fibrinogen < or = 5 g/L and CRP < or = 40 mg/L; P=0.09). CONCLUSIONS Plasma fibrinogen and serum CRP are associated with tumour characteristics. High values were associated with inability to achieve complete resection which may refine patient selection for thoracotomy when used with other staging modalities. Attempted resection may be justified in a patient of borderline fitness who has favourable plasma fibrinogen and serum CRP concentration, where a high resection rate is possible. As the relationship was with T stage rather than N stage it may be complimentary to PET scanning, which has only marginally better accuracy for T stage than CT scanning.
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Affiliation(s)
- J Mark Jones
- Division of Cardiac, Vascular and Thoracic Surgery, Royal Victoria Hospital, Belfast BT12 6BA, UK.
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Blackwell K, Hurwitz H, Liebérman G, Novotny W, Snyder S, Dewhirst M, Greenberg C. Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. Cancer 2004; 101:77-82. [PMID: 15221991 DOI: 10.1002/cncr.20336] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D-dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D-dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5-fluorouracil/leucovorin (5-FU/LV) with 5-FU/LV alone. METHODS At least one circulating D-dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D-dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression. RESULTS At trial enrollment, 86 of 104 patients (88%) had elevated D-dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D-dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, -0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D-dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D-dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D-dimer levels were the only predictors of overall survival (P < 0.05). CONCLUSIONS The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D-dimer levels should be incorporated into prognostic models, and D-dimer may represent a useful biomarker for patients treated with antiangiogenic agents.
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Affiliation(s)
- Kimberly Blackwell
- Division of Medical Oncology, Duke University Comprehensive Cancer Center, Durham, NC 27710, USA.
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Xu G, Zhang YL, Huang W. Relationship between plasma D-dimer levels and clinicopathologic parameters in resectable colorectal cancer patients. World J Gastroenterol 2004; 10:922-3. [PMID: 15040048 PMCID: PMC4727010 DOI: 10.3748/wjg.v10.i6.922] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To assess the clinical significance of the D-dimer levels and the relationship between plasma D-dimer levels and clinicopathologic parameters in operable colorectal cancer patients.
METHODS: The plasma levels of D-dimer were measured pre- and postoperatively in 35 patients with colorectal cancer, and 30 healthy subjects served as controls by the method of quantitative enzyme-linked immunosorbent assay (ELISA).
RESULTS: The mean preoperative plasma levels of D-dimer in the patients with colorectal cancer (1.06 ± 0.24 mg/L) were significantly higher than those of controls (0.33 ± 0.12 mg/L, P < 0.01). The D-dimer levels were remarkably elevated on the 1st day after operation (1.22 ± 0.55 mg/L, P < 0.01). On the 3rd day the level of D-dimer began to stepwise descend and on the 14th day nearly returned to control level. The preoperative levels of D-dimer were significantly correlated with the lymph node metastasis and Dukes stage but had no association with tumor location and the degree of differentiation. A stepwise increase in the mean D-dimer levels was found with increase of the tumor stage.
CONCLUSION: Hypercoagulation and higher fibrinolytic activities occur in patients with colorectal cancer. The operative trauma could enhance the fibrinolysis in the patients with colorectal cancer. The measurement of preoperative D-dimer levels is considered to be useful for predicting lymph node metastasis and stage of colorectal cancer.
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Affiliation(s)
- Gang Xu
- Institute of Gastroenterology, First Military Medical University, Guangzhou 510515, Guangdong Province, China.
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Salgado R, Benoy I, Weytjens R, Van Bockstaele D, Van Marck E, Huget P, Hoylaerts M, Vermeulen P, Dirix LY. Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer. Br J Cancer 2002; 87:1437-44. [PMID: 12454774 PMCID: PMC2376277 DOI: 10.1038/sj.bjc.6600655] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/12/2002] [Revised: 09/16/2002] [Accepted: 09/19/2002] [Indexed: 12/26/2022] Open
Abstract
The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis.
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Affiliation(s)
- R Salgado
- Angiogenesis Group, Oncology Center, St.-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk, Belgium
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