The D-dimer level predicts the postoperative prognosis in patients with non-small cell lung cancer

Autoři: Yuki Shiina aff001;  Takahiro Nakajima aff001;  Takayoshi Yamamoto aff001;  Kazuhisa Tanaka aff001;  Yuichi Sakairi aff001;  Hironobu Wada aff001;  Hidemi Suzuki aff001;  Ichiro Yoshino aff001
Působiště autorů: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



Carcinoma cells often modulate coagulation and fibrinolysis among cancer patients. Plasma dimerized plasmin fragment D (D-dimer) has been reported as a prognostic marker of various types of malignancies, including non-small cell lung cancer (NSCLC). However, the associations between the plasma D-dimer level and peripheral small NSCLC remain unclear.


Three hundred and sixty-two patients with NSCLC who underwent radical surgery were retrospectively reviewed. Patients who received anticoagulation therapy before surgery or who lacked preoperative D-dimer data were excluded. The other 235 patients were divided into a high D-dimer (over 1.0 μg/mL) group (HDD group, n = 47) and a normal D-dimer group (NDD group, n = 188) and investigated for their clinical characteristics, computed tomography (CT) findings, pathological findings, and clinical outcomes.


The mean D-dimer levels was 2.49±2.58 μg/ml in the HDD group and 0.42±0.23 μg/ml in the NDD group. The HDD group was characterized by a predominance of male gender, older age, pure solid appearance on chest CT, vascular invasion in pathology, and a large solid part of the tumor. The HDD group showed a worse overall survival, disease-free survival, and disease-specific survival than the NDD group (p<0.001, <0.001, <0.001, respectively). These survival features were also observed in p-Stage IA disease. There was no marked survival difference when tumors showed ground-glass opacity on CT.


In NSCLC patients with a solid tumor appearance on CT, high D-dimer levels predict a poor survival and early recurrence.

Klíčová slova:

Blood plasma – Carcinomas – Computed axial tomography – Histology – Non-small cell lung cancer – Opacity – Prognosis – Surgical and invasive medical procedures


1. Man YN, Wang YN, Hao J, Liu X, Liu C, Zhu C, et al. Pretreatment plasma D-dimer, fibrinogen, and platelet levels significantly impact prognosis in patients with epithelial ovarian cancer independently of venous thromboembolism. Int J Gynecol Cancer. 2015;25(1):24–32. Epub 2014/10/28. doi: 10.1097/IGC.0000000000000303 25347092

2. Fukumoto K, Taniguchi T, Usami N, Kawaguchi K, Fukui T, Ishiguro F, et al. Preoperative plasma D-dimer level is an independent prognostic factor in patients with completely resected non-small cell lung cancer. Surg Today. 2015;45(1):63–7. Epub 2014/05/02. doi: 10.1007/s00595-014-0894-4 24781600

3. Wang Z, Fu J, Diao D, Dang C. [Pre-operative plasma D-dimer level may predict the poor prognosis within one year after the surgery for non-small cell lung cancer]. Zhongguo Fei Ai Za Zhi. 2011;14(6):534–7. Epub 2011/06/08. doi: 10.3779/j.issn.1009-3419.2011.06.10 21645459

4. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110(6):1723–9. Epub 2007/05/15. doi: 10.1182/blood-2006-10-053736 17496204; PubMed Central PMCID: PMC1976377.

5. Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer—a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49(6):1404–13. Epub 2012/11/14. doi: 10.1016/j.ejca.2012.10.021 23146958

6. Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Importance of Ground Glass Opacity Component in Clinical Stage IA Radiologic Invasive Lung Cancer. Ann Thorac Surg. 2017;104(1):313–20. Epub 2017/04/24. doi: 10.1016/j.athoracsur.2017.01.076 28433219

7. Ando M FI, Ito M, Kobayashi T, Masuda M, Miyahara Y, Nakanishi N, Niwa A, Ohgi S, Tajima H, Ishibashi H, Kanaoka Y, Nakamura M, Sakuma M, Satoh T, Tanabe N, Yamada N, Yamashita M, Kuriyama T, Matsubara J, Nakano T, Ozaki Y, Sakata R. Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis (JCS 2009). Circ J. 2011;75(5):1258–81. Epub 2011/03/29. doi: 10.1253/circj.cj-88-0010 21441695

8. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60(3):615–22; discussion 22–3. Epub 1995/09/01. doi: 10.1016/0003-4975(95)00537-u 7677489

9. Okada M, Mimae T, Tsutani Y, Nakayama H, Okumura S, Yoshimura M, et al. Segmentectomy versus lobectomy for clinical stage IA lung adenocarcinoma. Annals of cardiothoracic surgery. 2014;3(2):153–9. Epub 2014/05/03. doi: 10.3978/j.issn.2225-319X.2014.02.10 24790838; PubMed Central PMCID: PMC3988306.

10. Bao F, Ye P, Yang Y, Wang L, Zhang C, Lv X, et al. Segmentectomy or lobectomy for early stage lung cancer: a meta-analysis. Eur J Cardiothorac Surg. 2014;46(1):1–7. Epub 2013/12/11. doi: 10.1093/ejcts/ezt554 24321996

11. Kamiya K, Hayashi Y, Douguchi J, Hashiguchi A, Yamada T, Izumi Y, et al. Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma. Mod Pathol. 2008;21(8):992–1001. Epub 2008/06/03. doi: 10.1038/modpathol.2008.79 18516041

12. Morimoto J, Nakajima T, Suzuki H, Nagato K, Iwata T, Yoshida S, et al. Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma. J Thorac Cardiovasc Surg. 2016;152(1):64-72.e1. Epub 2016/06/28. doi: 10.1016/j.jtcvs.2016.03.088 27343907

13. Ujiie H, Kadota K, Chaft JE, Buitrago D, Sima CS, Lee MC, et al. Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival. J Clin Oncol. 2015;33(26):2877–84. Epub 2015/08/12. doi: 10.1200/JCO.2015.60.9818 26261257; PubMed Central PMCID: PMC4554749.

14. Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Prognostic impact of a ground glass opacity component in the clinical T classification of non-small cell lung cancer. J Thorac Cardiovasc Surg. 2017;154(6):2102-10.e1. Epub 2017/09/28. doi: 10.1016/j.jtcvs.2017.08.037 28947198

15. Ma X, Li Y, Zhang J, Huang J, Liu L. Prognostic role of D-dimer in patients with lung cancer: a meta-analysis. Tumour Biol. 2014;35(3):2103–9. Epub 2013/10/12. doi: 10.1007/s13277-013-1279-9 24114016

16. Zhu LR, Li J, Chen P, Jiang Q, Tang XP. Clinical significance of plasma fibrinogen and D-dimer in predicting the chemotherapy efficacy and prognosis for small cell lung cancer patients. Clin Transl Oncol. 2016;18(2):178–88. Epub 2015/07/18. doi: 10.1007/s12094-015-1350-7 26184726

17. Inal T, Anar C, Polat G, Unsal I, Halilcolar H. The prognostic value of D-dimer in lung cancer. Clin Respir J. 2015;9(3):305–13. Epub 2014/04/12. doi: 10.1111/crj.12144 24720709

18. Gao XL, Wang SS, Cao DB, Liu W. The role of plasma D-dimer levels for predicting lymph node and mediastinal lymph node involvement in non-small cell lung cancer. Clin Respir J. 2018. Epub 2018/03/03. doi: 10.1111/crj.12786 29498801

19. Stender MT, Larsen TB, Sorensen HT, Thorlacius-Ussing O. Preoperative plasma D-dimer predicts 1-year survival in colorectal cancer patients with absence of venous thromboembolism (VTE): a prospective clinical cohort study. J Thromb Haemost. 2012;10(10):2027–31. Epub 2012/08/21. doi: 10.1111/j.1538-7836.2012.04887.x 22900573

20. Stender MT, Larsen AC, Sall M, Thorlacius-Ussing O. D-Dimer predicts prognosis and non-resectability in patients with pancreatic cancer: a prospective cohort study. Blood Coagul Fibrinolysis. 2016;27(5):597–601. Epub 2016/05/18. doi: 10.1097/MBC.0000000000000559 27182687

21. Lal I, Dittus K, Holmes CE. Platelets, coagulation and fibrinolysis in breast cancer progression. Breast Cancer Res. 2013;15(4):207. Epub 2013/08/03. doi: 10.1186/bcr3425 23905544; PubMed Central PMCID: PMC3979075.

22. Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost. 2011;9(2):237–49. Epub 2010/11/03. doi: 10.1111/j.1538-7836.2010.04131.x 21040448

23. Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69(19):7775–83. Epub 2009/09/10. doi: 10.1158/0008-5472.CAN-09-2123 19738039

24. Han B, Nakamura M, Mori I, Nakamura Y, Kakudo K. Urokinase-type plasminogen activator system and breast cancer (Review). Oncol Rep. 2005;14(1):105–12. Epub 2005/06/10. 15944776

25. Even-Ram S, Uziely B, Cohen P, Grisaru-Granovsky S, Maoz M, Ginzburg Y, et al. Thrombin receptor overexpression in malignant and physiological invasion processes. Nat Med. 1998;4(8):909–14. Epub 1998/08/13. doi: 10.1038/nm0898-909 9701242

26. Hu L, Lee M, Campbell W, Perez-Soler R, Karpatkin S. Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. Blood. 2004;104(9):2746–51. Epub 2004/07/22. doi: 10.1182/blood-2004-03-1047 15265791

Článek vyšel v časopise


2019 Číslo 12
Nejčtenější tento týden