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D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy.

Go SI, Lee MJ, Lee WS, Choi HJ, Lee US, Kim RB, Kang MH, Kim HG, Lee GW, Kang JH, Lee JH, Kim SJ - Medicine (Baltimore) (2015)

Bottom Line: D-dimer levels were assessed before CTx and at the first response evaluation after CTx.The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019).At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease.In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009).

View Article: PubMed Central - PubMed

Affiliation: From the Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (S-IG, MJL, WSL, HJC, USL, MHK, H-GK, G-WL, JHK); Department of Preventive Medicine and Environmental Health Center, Gyeongsang National University School of Medicine, Jinju, Korea (RBK), Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (JHL); and Department of Laboratory Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (SJK).

ABSTRACT
Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level.We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx.The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009). The lower D-dimer levels (<1.0 μg/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (P = 0.037).This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.

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Related in: MedlinePlus

Mechanisms for cancer-induced hypercoagulation and consequential D-dimer formation. Cancer cells promote a hypercoagulable status and activate the hemostatic system. The cancer cells induce the hypercoagulable status by cell-to-cell interaction with endothelial cells, direct release of TF and CP, production of cytokines such as IL-1and TNF, and activation of monocyte, macrophage, and platelet. CP = cancer procoagulants, IL-1 = interleukin-1, PAI = plasminogen activator inhibitor, TF = tissue factor, TNF = tumor necrosis factor.
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Figure 1: Mechanisms for cancer-induced hypercoagulation and consequential D-dimer formation. Cancer cells promote a hypercoagulable status and activate the hemostatic system. The cancer cells induce the hypercoagulable status by cell-to-cell interaction with endothelial cells, direct release of TF and CP, production of cytokines such as IL-1and TNF, and activation of monocyte, macrophage, and platelet. CP = cancer procoagulants, IL-1 = interleukin-1, PAI = plasminogen activator inhibitor, TF = tissue factor, TNF = tumor necrosis factor.

Mentions: The cause of cancer death is mostly due to cancer progression, but thromboembolism also accounts for 10% to 20%.6 Levitan et al7 reported that the risk for venous thromboembolism (VTE) in cancer patients is 6 times higher than the control group. It is well known that gastric cancer has a high risk of developing VTE in particular.8 VTE in cancer patients is typically associated with plasma hypercoagulability, endothelial damage, and stasis of blood flow.9 The possible mechanisms of hypercoagulability are shown in Figure 1. The clotting process is exacerbated by direct interaction between cancer cells and the endothelial cells, by activating blood cells such as monocyte, macrophage, and platelet, and/or by secreting tissue factor, cancer procoagulants, and cytokines from cancer cells.10,11 Interestingly, these coagulation products are also associated with the growth, progression, metastasis, and angiogenesis of cancer.11,12 Therefore, thromboembolism is not only a direct cause of death in cancer patients but also closely related to the death from cancer progression. This is supported by the reports that the coagulation abnormality is associated with low survival rate in cancer patients.8,13


D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy.

Go SI, Lee MJ, Lee WS, Choi HJ, Lee US, Kim RB, Kang MH, Kim HG, Lee GW, Kang JH, Lee JH, Kim SJ - Medicine (Baltimore) (2015)

Mechanisms for cancer-induced hypercoagulation and consequential D-dimer formation. Cancer cells promote a hypercoagulable status and activate the hemostatic system. The cancer cells induce the hypercoagulable status by cell-to-cell interaction with endothelial cells, direct release of TF and CP, production of cytokines such as IL-1and TNF, and activation of monocyte, macrophage, and platelet. CP = cancer procoagulants, IL-1 = interleukin-1, PAI = plasminogen activator inhibitor, TF = tissue factor, TNF = tumor necrosis factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554111&req=5

Figure 1: Mechanisms for cancer-induced hypercoagulation and consequential D-dimer formation. Cancer cells promote a hypercoagulable status and activate the hemostatic system. The cancer cells induce the hypercoagulable status by cell-to-cell interaction with endothelial cells, direct release of TF and CP, production of cytokines such as IL-1and TNF, and activation of monocyte, macrophage, and platelet. CP = cancer procoagulants, IL-1 = interleukin-1, PAI = plasminogen activator inhibitor, TF = tissue factor, TNF = tumor necrosis factor.
Mentions: The cause of cancer death is mostly due to cancer progression, but thromboembolism also accounts for 10% to 20%.6 Levitan et al7 reported that the risk for venous thromboembolism (VTE) in cancer patients is 6 times higher than the control group. It is well known that gastric cancer has a high risk of developing VTE in particular.8 VTE in cancer patients is typically associated with plasma hypercoagulability, endothelial damage, and stasis of blood flow.9 The possible mechanisms of hypercoagulability are shown in Figure 1. The clotting process is exacerbated by direct interaction between cancer cells and the endothelial cells, by activating blood cells such as monocyte, macrophage, and platelet, and/or by secreting tissue factor, cancer procoagulants, and cytokines from cancer cells.10,11 Interestingly, these coagulation products are also associated with the growth, progression, metastasis, and angiogenesis of cancer.11,12 Therefore, thromboembolism is not only a direct cause of death in cancer patients but also closely related to the death from cancer progression. This is supported by the reports that the coagulation abnormality is associated with low survival rate in cancer patients.8,13

Bottom Line: D-dimer levels were assessed before CTx and at the first response evaluation after CTx.The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019).At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease.In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009).

View Article: PubMed Central - PubMed

Affiliation: From the Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (S-IG, MJL, WSL, HJC, USL, MHK, H-GK, G-WL, JHK); Department of Preventive Medicine and Environmental Health Center, Gyeongsang National University School of Medicine, Jinju, Korea (RBK), Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (JHL); and Department of Laboratory Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea (SJK).

ABSTRACT
Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level.We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx.The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009). The lower D-dimer levels (<1.0 μg/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (P = 0.037).This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.

Show MeSH
Related in: MedlinePlus