Clinical significance of coagulation factors in operable colorectal cancer

Lee,Suee; Huh,Seok Jae; Oh,Sung Yong; Koh,Myeong Seok; Kim,Sung‑Hyun; Lee,Ji Hyun; Han,Jin Young; Choi,Hong Jo; Kim,Su Jin; Kim,Hyo‑Jin

doi:10.3892/ol.2017.6058

Clinical significance of coagulation factors in operable colorectal cancer

Authors:
- Suee Lee
- Seok Jae Huh
- Sung Yong Oh
- Myeong Seok Koh
- Sung‑Hyun Kim
- Ji Hyun Lee
- Jin Young Han
- Hong Jo Choi
- Su Jin Kim
- Hyo‑Jin Kim
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Affiliations: Department of Internal Medicine, Dong‑A University College of Medicine, Busan 49201, Republic of Korea, Department of Laboratory Medicine, Dong‑A University College of Medicine, Busan 49201, Republic of Korea, Department of Surgery, Dong‑A University College of Medicine, Busan 49201, Republic of Korea, Department of Pathology, Dong‑A University College of Medicine, Busan 49201, Republic of Korea
Published online on: April 20, 2017 https://doi.org/10.3892/ol.2017.6058
Pages: 4669-4674
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D‑dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28‑84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D‑dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper‑fibrinogenemia (≥327 mg/dl), high D‑dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D‑dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.

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1	Donati MB and Lorenzet R: Thrombosis and cancer: 40 years of research. Thromb Res. 129:348–352. 2012. View Article : Google Scholar : PubMed/NCBI
2	Wojtukiewicz MZ, Sierko E, Klementt P and Rak J: The hemostatic system and angiogenesis in malignancy. Neoplasia. 3:371–384. 2001. View Article : Google Scholar : PubMed/NCBI
3	Falanga A, Marchetti M and Vignoli A: Coagulation and cancer: Biological and clinical aspects. J Thromb Haemost. 11:223–233. 2013. View Article : Google Scholar : PubMed/NCBI
4	Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI
5	Falanga A, Russo L and Milesi V: The coagulopathy of cancer. Curr Opin Hematol. 21:423–429. 2014. View Article : Google Scholar : PubMed/NCBI
6	Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, Tatsuta M and Satomi T: Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 9:287–291. 2002. View Article : Google Scholar : PubMed/NCBI
7	Yamashita H, Kitayama J and Nagawa H: Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol. 35:595–600. 2005. View Article : Google Scholar : PubMed/NCBI
8	Yamashita H, Kitayama J, Kanno N, Yatomi Y and Nagawa H: Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer. 6:1472006. View Article : Google Scholar : PubMed/NCBI
9	Yamashita H, Kitayama J, Ishikawa M and Nagawa H: Tissue factor expression is a clinical indicator of lymphatic metastasis and poor prognosis in gastric cancer with intestinal phenotype. J Surg Oncol. 95:324–331. 2007. View Article : Google Scholar : PubMed/NCBI
10	Lee SE, Lee JH, Ryu KW, Nam BH, Cho SJ, Lee JY, Kim CG, Choi IJ, Kook MC, Park SR and Kim YW: Preoperative plasma fibrinogen level is a useful predictor of adjacent organ involvement in patients with advanced gastric cancer. J Gastric Cancer. 12:81–87. 2012. View Article : Google Scholar : PubMed/NCBI
11	Khorana AA, Ahrendt SA, Ryan CK, Francis CW, Hruban RH, Hu YC, Hostetter G, Harvey J and Taubman MB: Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res. 13:2870–2875. 2007. View Article : Google Scholar : PubMed/NCBI
12	Joanne LY, May L, Lhotak V, Shahrzad S, Shirasawa S, Weitz JI, Coomber BL, Mackman N and Rak JW: Oncogenic events regulate tissue factor expression in colorectal cancer cells: Implications for tumor progression and angiogenesis. Blood. 105:1734–1741. 2005. View Article : Google Scholar : PubMed/NCBI
13	Oya M, Akiyama Y, Okuyama T and Ishikawa H: High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer. Jpn J Clin Oncol. 31:388–394. 2001. View Article : Google Scholar : PubMed/NCBI
14	Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, et al: Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 69:491–497. 1980. View Article : Google Scholar : PubMed/NCBI
15	UICC, . TNM Classification of Malignant Tumours. 7th. Wiley & Liss; New York: 2009
16	Gouin-Thibault I and Samama MM: Laboratory diagnosis of the thrombophilic state in cancer patients. Semin Thromb Hemost. 25:167–172. 1999. View Article : Google Scholar : PubMed/NCBI
17	Lima LG and Monteiro RQ: Activation of blood coagulation in cancer: Implications for tumour progression. Biosci Rep. 33:e000642013. View Article : Google Scholar : PubMed/NCBI
18	Balkwill F and Mantovani A: Inflammation and cancer: Back to Virchow? Lancet. 357:539–545. 2001. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Wang E, Kavanagh JJ and Freedman RS: Ovarian cancer, the coagulation pathway, and inflammation. J Transl Med. 3:252005. View Article : Google Scholar : PubMed/NCBI
20	Tang L, Liu K, Wang J, Wang C, Zhao P and Liu J: High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer. J Surg Oncol. 102:428–432. 2010. View Article : Google Scholar : PubMed/NCBI
21	Tennent GA, Brennan SO, Stangou AJ, O'Grady J, Hawkins PN and Pepys MB: Human plasma fibrinogen is synthesized in the liver. Blood. 109:1971–1974. 2007. View Article : Google Scholar : PubMed/NCBI
22	Sahni A, SimpsonHaidaris P, Sahni S, Vaday G and Francis C: Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost. 6:176–183. 2008. View Article : Google Scholar : PubMed/NCBI
23	Guadiz G, Sporn LA and Simpson-Haidaris PJ: Thrombin cleavage-independent deposition of fibrinogen in extracellular matrices. Blood. 90:2644–2653. 1997.PubMed/NCBI
24	Takeuchi H, Ikeuchi S, Kitagawa Y, Shimada A, Oishi T, Isobe Y, Kubochi K, Kitajima M and Matsumoto S: Pretreatment plasma fibrinogen level correlates with tumor progression and metastasis in patients with squamous cell carcinoma of the esophagus. J Gastroenterol Hepatol. 22:2222–2227. 2007. View Article : Google Scholar : PubMed/NCBI
25	Polterauer S, Seebacher V, Hefler-Frischmuth K, Grimm C, Heinze G, Tempfer C, Reinthaller A and Hefler L: Fibrinogen plasma levels are an independent prognostic parameter in patients with cervical cancer. Am J Obstet Gynecol. 200:647.e1–e7. 2009. View Article : Google Scholar
26	Polterauer S, Grimm C, Seebacher V, Concin N, Marth C, Tomovski C, Husslein H, Leipold H, Hefler-Frischmuth K, Tempfer C, et al: Plasma fibrinogen levels and prognosis in patients with ovarian cancer: A multicenter study. Oncologist. 14:979–985. 2009. View Article : Google Scholar : PubMed/NCBI
27	Li Y, Wei S, Wang J, Hong L, Cui L and 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. 17:789–796. 2014.(In Chinese). PubMed/NCBI
28	Ma Y, Qian Y and Lv W: The correlation between plasma fibrinogen levels and the clinical features of patients with ovarian carcinoma. J Int Med Res. 35:678–684. 2007. View Article : Google Scholar : PubMed/NCBI
29	Liu L, Zhang X, Yan B, Gu Q, Zhang X, Jiao J, Sun D, Wang N and Yue X: Elevated plasma D-dimer levels correlate with long term survival of gastric cancer patients. PloS One. 9:e905472014. View Article : Google Scholar : PubMed/NCBI
30	Yamamoto M, Yoshinaga K, Matsuyama A, Iwasa T, Osoegawa A, Tsujita E, Yamashita Y, Tsutsui S and Ishida T: Plasma D-dimer level as a mortality predictor in patients with advanced or recurrent colorectal cancer. Oncology. 83:10–15. 2012. View Article : Google Scholar : PubMed/NCBI
31	Fukumoto K, Taniguchi T, Usami N, Kawaguchi K, Fukui T, Ishiguro F, Nakamura S and Yokoi K: The preoperative plasma D-dimer level is an independent prognostic factor in patients with completely resected non-small cell lung cancer. Surg Today. 45:63–67. 2015. View Article : Google Scholar : PubMed/NCBI
32	İnal T, Anar C, Polat G, Ünsal İ and Halilçolar H: The prognostic value of D-dimer in lung cancer. Clin Respir J. 9:305–313. 2015. View Article : Google Scholar : PubMed/NCBI
33	Man YN, Wang YN, Hao J, Liu X, Liu C, Zhu C and Wu XZ: 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. 25:24–32. 2015. View Article : Google Scholar : PubMed/NCBI
34	Blackwell K, Haroon Z, Broadwater G, Berry D, Harris L, Iglehart JD, Dewhirst M and Greenberg C: Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status. J Clin Oncol. 18:600–608. 2000. View Article : Google Scholar : PubMed/NCBI
35	Li FX, Wei LJ, Zhang H, Li SX and Liu JT: Significance of thrombocytosis in clinicopathologic characteristics and prognosis of gastric cancer. Asian Pac J Cancer Prev. 15:6511–6517. 2014. View Article : Google Scholar : PubMed/NCBI
36	Li Y, Miao LY, Xiao YL, Cai HR and Zhang DP: Elevated platelets enhance cancer cell migration, promote hematogenous metastasis and associate with a poor prognosis in advanced non-small cell lung cancer cases. Asian Pac J Cancer Prev. 15:139–143. 2014. View Article : Google Scholar : PubMed/NCBI
37	Heng S and Benjapibal M: Preoperative thrombocytosis and poor prognostic factors in endometrial cancer. Asian Pac J Cancer Prev. 15:10231–10236. 2014. View Article : Google Scholar : PubMed/NCBI
38	Sasaki K, Kawai K, Tsuno NH, Sunami E and Kitayama J: Impact of preoperative thrombocytosis on the survival of patients with primary colorectal cancer. World J Surg. 36:192–200. 2012. View Article : Google Scholar : PubMed/NCBI
39	Di Micco P, Romano M, Niglio A, Nozzolillo P, Federico A, Petronella P, Nunziata L, Di Micco B and Torella R: Alteration of haemostasis in non-metastatic gastric cancer. Dig Liver Dis. 33:546–550. 2001. View Article : Google Scholar : PubMed/NCBI
40	Ferrigno D, Buccheri G and Ricca I: Prognostic significance of blood coagulation tests in lung cancer. Eur Respir J. 17:667–673. 2001. View Article : Google Scholar : PubMed/NCBI
41	Kılıc M, Yoldas O, Keskek M, Ertan T, Tez M, Gocmen E and Koc M: Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis. 10:238–241. 2008. View Article : Google Scholar : PubMed/NCBI
42	Südhoff T and Schneider W: Fibrinolytic mechanisms in tumor growth and spreading. Clin Investig. 70:631–636. 1992. View Article : Google Scholar : PubMed/NCBI
43	Lykke J and Nielsen HJ: Haemostatic alterations in colorectal cancer: Perspectives for future treatment. J Surg Oncol. 88:269–275. 2004. View Article : Google Scholar : PubMed/NCBI
44	Bugge TH, Kombrinck KW, Xiao Q, Holmbäck K, Daugherty CC, Witte DP and Degen JL: Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice. Blood. 90:4522–4531. 1997.PubMed/NCBI
45	Svendsen MN, Werther K, Nielsen HJ and Kristjansen PE: VEGF and tumour angiogenesis. Impact of surgery, wound healing, inflammation and blood transfusion. Scand J Gastroenterol. 37:373–379. 2002. View Article : Google Scholar : PubMed/NCBI