Skip to main content
Top
Published in: International Journal of Colorectal Disease 1/2011

01-01-2011 | Original Article

Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer

Authors: Kazushige Kawai, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Hirokazu Nagawa

Published in: International Journal of Colorectal Disease | Issue 1/2011

Login to get access

Abstract

Purpose

Although hyperfibrinogenemia has been reported in patients with colorectal cancer, neither its clinical implications nor the effect of chemoradiotherapy (CRT) on the fibrinogen levels have been fully investigated. We investigated the clinical significance of pre- and post-CRT fibrinogen levels in patients with rectal cancer.

Methods

The medical records of 82 patients with rectal cancer, who had received CRT followed by surgical resection, were retrospectively reviewed. The correlation between the clinicopathological variables and the pre- and post-CRT plasma fibrinogen levels, and that between the changes of fibrinogen, C-reactive protein (CRP), or carcinoembryonic antigen (CEA) levels after CRT and the pathological tumor regression grading was analyzed. Furthermore, the impact of post-CRT fibrinogen levels on the prognosis of these patients was assessed.

Results

Plasma fibrinogen markedly decreased after CRT. The post-CRT fibrinogen level significantly correlated with lymphatic invasion, venous invasion, tumor size, depth of invasion, and the pathological tumor regression grading. The CRT-induced pathological tumor regression grading well correlated with the decrease of fibrinogen level, but not with that of CRP or CEA. Furthermore, patients with high post-CRT fibrinogen had significantly shorter disease-free survival.

Conclusions

Reduction of plasma fibrinogen induced by CRT should be a promising biomarker for evaluating the efficacy of CRT in rectal cancer patients.
Literature
1.
go back to reference Tomimaru Y, Yano M, Takachi K, Kishi K, Miyashiro I, Ohue M et al (2006) Plasma D-dimer levels show correlation with number of lymph node metastases in patients with esophageal cancer. J Am Coll Surg 202(1):139–145CrossRefPubMed Tomimaru Y, Yano M, Takachi K, Kishi K, Miyashiro I, Ohue M et al (2006) Plasma D-dimer levels show correlation with number of lymph node metastases in patients with esophageal cancer. J Am Coll Surg 202(1):139–145CrossRefPubMed
2.
go back to reference Altiay G, Ciftci A, Demir M, Kocak Z, Sut N, Tabakoglu E et al (2007) High plasma D-dimer level is associated with decreased survival in patients with lung cancer. Clin Oncol R Coll Radiol 19(7):494–498PubMed Altiay G, Ciftci A, Demir M, Kocak Z, Sut N, Tabakoglu E et al (2007) High plasma D-dimer level is associated with decreased survival in patients with lung cancer. Clin Oncol R Coll Radiol 19(7):494–498PubMed
3.
go back to reference Kilic M, Yoldas O, Keskek M, Ertan T, Tez M, Gocmen E et al (2008) Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis 10(3):238–241CrossRefPubMed Kilic M, Yoldas O, Keskek M, Ertan T, Tez M, Gocmen E et al (2008) Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis 10(3):238–241CrossRefPubMed
4.
go back to reference Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R et al (1999) Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Med Baltim 78(5):285–291CrossRef Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R et al (1999) Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Med Baltim 78(5):285–291CrossRef
5.
go back to reference Yamashita H, Kitayama J, Nagawa H (2005) Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol 35(10):595–600CrossRefPubMed Yamashita H, Kitayama J, Nagawa H (2005) Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol 35(10):595–600CrossRefPubMed
6.
go back to reference Yamashita H, Kitayama J, Kanno N, Yatomi Y, Nagawa H (2006) Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer 6:147CrossRefPubMed Yamashita H, Kitayama J, Kanno N, Yatomi Y, Nagawa H (2006) Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer 6:147CrossRefPubMed
7.
go back to reference Yamashita H, Kitayama J, Taguri M, Nagawa H (2009) Effect of preoperative hyperfibrinogenemia on recurrence of colorectal cancer without a systemic inflammatory response. World J Surg 33(6):1298–1305CrossRefPubMed Yamashita H, Kitayama J, Taguri M, Nagawa H (2009) Effect of preoperative hyperfibrinogenemia on recurrence of colorectal cancer without a systemic inflammatory response. World J Surg 33(6):1298–1305CrossRefPubMed
8.
go back to reference ten Cate H, Falanga A (2008) Overview of the postulated mechanisms linking cancer and thrombosis. Pathophysiol Haemost Thromb 36(3–4):122–130PubMed ten Cate H, Falanga A (2008) Overview of the postulated mechanisms linking cancer and thrombosis. Pathophysiol Haemost Thromb 36(3–4):122–130PubMed
9.
go back to reference Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740CrossRefPubMed Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740CrossRefPubMed
10.
go back to reference Watanabe T, Nagawa H (2004) Sphincter preservation in locally advanced rectal cancer due to the addition of continuous infusion 5-FU to preoperative radiation therapy or advances in surgical techniques? Int J Radiat Oncol Biol Phys 59(2):618, author reply 618PubMed Watanabe T, Nagawa H (2004) Sphincter preservation in locally advanced rectal cancer due to the addition of continuous infusion 5-FU to preoperative radiation therapy or advances in surgical techniques? Int J Radiat Oncol Biol Phys 59(2):618, author reply 618PubMed
11.
go back to reference Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355(11):1114–1123CrossRefPubMed Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355(11):1114–1123CrossRefPubMed
12.
go back to reference Fu CG, Tominaga O, Nagawa H, Nita ME, Masaki T, Ishimaru G et al (1998) Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients. Dis Colon Rectum 41(1):68–74CrossRefPubMed Fu CG, Tominaga O, Nagawa H, Nita ME, Masaki T, Ishimaru G et al (1998) Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients. Dis Colon Rectum 41(1):68–74CrossRefPubMed
13.
go back to reference Marquardt F, Rodel F, Capalbo G, Weiss C, Rodel C (2009) Molecular targeted treatment and radiation therapy for rectal cancer. Strahlenther Onkol 185(6):371–378CrossRefPubMed Marquardt F, Rodel F, Capalbo G, Weiss C, Rodel C (2009) Molecular targeted treatment and radiation therapy for rectal cancer. Strahlenther Onkol 185(6):371–378CrossRefPubMed
14.
go back to reference Kuremsky JG, Tepper JE, McLeod HL (2009) Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 74(3):673–688CrossRefPubMed Kuremsky JG, Tepper JE, McLeod HL (2009) Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 74(3):673–688CrossRefPubMed
15.
go back to reference Kikuchi M, Mikami T, Sato T, Tokuyama W, Araki K, Watanabe M et al (2009) High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Br J Cancer 101(1):116–123CrossRefPubMed Kikuchi M, Mikami T, Sato T, Tokuyama W, Araki K, Watanabe M et al (2009) High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Br J Cancer 101(1):116–123CrossRefPubMed
16.
go back to reference Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N et al (2002) The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 95(6):1199–1205CrossRefPubMed Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N et al (2002) The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 95(6):1199–1205CrossRefPubMed
17.
go back to reference Komuro Y, Watanabe T, Tsurita G, Muto T, Nagawa H (2005) Evaluating the combination of molecular prognostic factors in tumor radiosensitivity in rectal cancer. Hepatogastroenterology 52(63):666–671PubMed Komuro Y, Watanabe T, Tsurita G, Muto T, Nagawa H (2005) Evaluating the combination of molecular prognostic factors in tumor radiosensitivity in rectal cancer. Hepatogastroenterology 52(63):666–671PubMed
18.
go back to reference Komuro Y, Watanabe T, Tsurita G, Muto T, Nagawa H (2005) Expression pattern of telomerase reverse transcriptase in rectal carcinoma predicts tumor radiosensitivity, local recurrence and disease-free survival. Hepatogastroenterology 52(64):985–989PubMed Komuro Y, Watanabe T, Tsurita G, Muto T, Nagawa H (2005) Expression pattern of telomerase reverse transcriptase in rectal carcinoma predicts tumor radiosensitivity, local recurrence and disease-free survival. Hepatogastroenterology 52(64):985–989PubMed
19.
go back to reference Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12(1):19–23CrossRefPubMed Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12(1):19–23CrossRefPubMed
20.
go back to reference Marchena J, Acosta MA, Garcia-Anguiano F, Simpson H, Cruz F (2003) Use of the preoperative levels of CEA in patients with colorectal cancer. Hepatogastroenterology 50(52):1017–1020PubMed Marchena J, Acosta MA, Garcia-Anguiano F, Simpson H, Cruz F (2003) Use of the preoperative levels of CEA in patients with colorectal cancer. Hepatogastroenterology 50(52):1017–1020PubMed
21.
go back to reference Redman CM, Xia H (2001) Fibrinogen biosynthesis. Assembly, intracellular degradation, and association with lipid synthesis and secretion. Ann NY Acad Sci 936:480–495CrossRefPubMed Redman CM, Xia H (2001) Fibrinogen biosynthesis. Assembly, intracellular degradation, and association with lipid synthesis and secretion. Ann NY Acad Sci 936:480–495CrossRefPubMed
22.
go back to reference Martini WZ (2009) Fibrinogen metabolic responses to trauma. Scand J Trauma Resusc Emerg Med 17(1):2CrossRefPubMed Martini WZ (2009) Fibrinogen metabolic responses to trauma. Scand J Trauma Resusc Emerg Med 17(1):2CrossRefPubMed
23.
go back to reference Collen D, Tytgat GN, Claeys H, Piessens R (1972) Metabolism and distribution of fibrinogen. I. Fibrinogen turnover in physiological conditions in humans. Br J Haematol 22(6):681–700CrossRefPubMed Collen D, Tytgat GN, Claeys H, Piessens R (1972) Metabolism and distribution of fibrinogen. I. Fibrinogen turnover in physiological conditions in humans. Br J Haematol 22(6):681–700CrossRefPubMed
24.
go back to reference Zhang Z, Fuller GM (2000) Interleukin 1beta inhibits interleukin 6-mediated rat gamma fibrinogen gene expression. Blood 96(10):3466–3472PubMed Zhang Z, Fuller GM (2000) Interleukin 1beta inhibits interleukin 6-mediated rat gamma fibrinogen gene expression. Blood 96(10):3466–3472PubMed
25.
go back to reference Albrecht U, Yang X, Asselta R, Keitel V, Tenchini ML, Ludwig S et al (2007) Activation of NF-kappaB by IL-1beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen gene. Cell Signal 19(9):1866–1878CrossRefPubMed Albrecht U, Yang X, Asselta R, Keitel V, Tenchini ML, Ludwig S et al (2007) Activation of NF-kappaB by IL-1beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen gene. Cell Signal 19(9):1866–1878CrossRefPubMed
26.
go back to reference Grieninger G, Plant PW, Liang TJ, Kalb RG, Amrani D, Mosesson MW et al (1983) Hormonal regulation of fibrinogen synthesis in cultured hepatocytes. Ann NY Acad Sci 408:469–489CrossRefPubMed Grieninger G, Plant PW, Liang TJ, Kalb RG, Amrani D, Mosesson MW et al (1983) Hormonal regulation of fibrinogen synthesis in cultured hepatocytes. Ann NY Acad Sci 408:469–489CrossRefPubMed
27.
go back to reference Seebacher V, Polterauer S, Grimm C, Husslein H, Leipold H, Hefler-Frischmuth K et al (2010) The prognostic value of plasma fibrinogen levels in patients with endometrial cancer: a multi-centre trial. Br J Cancer 102(6):952–956CrossRefPubMed Seebacher V, Polterauer S, Grimm C, Husslein H, Leipold H, Hefler-Frischmuth K et al (2010) The prognostic value of plasma fibrinogen levels in patients with endometrial cancer: a multi-centre trial. Br J Cancer 102(6):952–956CrossRefPubMed
28.
go back to reference Rybarczyk BJ, Simpson-Haidaris PJ (2000) Fibrinogen assembly, secretion, and deposition into extracellular matrix by MCF-7 human breast carcinoma cells. Cancer Res 60(7):2033–2039PubMed Rybarczyk BJ, Simpson-Haidaris PJ (2000) Fibrinogen assembly, secretion, and deposition into extracellular matrix by MCF-7 human breast carcinoma cells. Cancer Res 60(7):2033–2039PubMed
29.
go back to reference Yamaguchi T, Yamamoto Y, Yokota S, Nakagawa M, Ito M, Ogura T (1998) Involvement of interleukin-6 in the elevation of plasma fibrinogen levels in lung cancer patients. Jpn J Clin Oncol 28(12):740–744CrossRefPubMed Yamaguchi T, Yamamoto Y, Yokota S, Nakagawa M, Ito M, Ogura T (1998) Involvement of interleukin-6 in the elevation of plasma fibrinogen levels in lung cancer patients. Jpn J Clin Oncol 28(12):740–744CrossRefPubMed
30.
go back to reference Panes J, Granger DN (1996) Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology 111(4):981–989CrossRefPubMed Panes J, Granger DN (1996) Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology 111(4):981–989CrossRefPubMed
31.
go back to reference Debucquoy A, Goethals L, Geboes K, Roels S, McBride WH, Haustermans K (2006) Molecular responses of rectal cancer to preoperative chemoradiation. Radiother Oncol 80(2):172–177CrossRefPubMed Debucquoy A, Goethals L, Geboes K, Roels S, McBride WH, Haustermans K (2006) Molecular responses of rectal cancer to preoperative chemoradiation. Radiother Oncol 80(2):172–177CrossRefPubMed
32.
go back to reference Wichmann MW, Meyer G, Adam M, Hochtlen-Vollmar W, Angele MK, Schalhorn A et al (2003) Detrimental immunologic effects of preoperative chemoradiotherapy in advanced rectal cancer. Dis Colon Rectum 46(7):875–887CrossRefPubMed Wichmann MW, Meyer G, Adam M, Hochtlen-Vollmar W, Angele MK, Schalhorn A et al (2003) Detrimental immunologic effects of preoperative chemoradiotherapy in advanced rectal cancer. Dis Colon Rectum 46(7):875–887CrossRefPubMed
33.
go back to reference Simpson-Haidaris PJ, Rybarczyk B (2001) Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein. Ann NY Acad Sci 936:406–425CrossRefPubMed Simpson-Haidaris PJ, Rybarczyk B (2001) Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein. Ann NY Acad Sci 936:406–425CrossRefPubMed
34.
go back to reference Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL (2002) Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res 62(23):6966–6972PubMed Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL (2002) Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res 62(23):6966–6972PubMed
35.
go back to reference Zheng S, Shen J, Jiao Y, Liu Y, Zhang C, Wei M et al (2009) Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci 100(5):859–865CrossRefPubMed Zheng S, Shen J, Jiao Y, Liu Y, Zhang C, Wei M et al (2009) Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci 100(5):859–865CrossRefPubMed
36.
go back to reference Brown NJ, Staton CA, Rodgers GR, Corke KP, Underwood JC, Lewis CE (2002) Fibrinogen E fragment selectively disrupts the vasculature and inhibits the growth of tumours in a syngeneic murine model. Br J Cancer 86(11):1813–1816CrossRefPubMed Brown NJ, Staton CA, Rodgers GR, Corke KP, Underwood JC, Lewis CE (2002) Fibrinogen E fragment selectively disrupts the vasculature and inhibits the growth of tumours in a syngeneic murine model. Br J Cancer 86(11):1813–1816CrossRefPubMed
37.
go back to reference Akakura N, Hoogland C, Takada YK, Saegusa J, Ye X, Liu FT et al (2006) The COOH-terminal globular domain of fibrinogen gamma chain suppresses angiogenesis and tumor growth. Cancer Res 66(19):9691–9697CrossRefPubMed Akakura N, Hoogland C, Takada YK, Saegusa J, Ye X, Liu FT et al (2006) The COOH-terminal globular domain of fibrinogen gamma chain suppresses angiogenesis and tumor growth. Cancer Res 66(19):9691–9697CrossRefPubMed
Metadata
Title
Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer
Authors
Kazushige Kawai
Joji Kitayama
Nelson H. Tsuno
Eiji Sunami
Hirokazu Nagawa
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 1/2011
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-010-1054-y

Other articles of this Issue 1/2011

International Journal of Colorectal Disease 1/2011 Go to the issue