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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma

Authors: Wenjie Jiao, Jing Xu, Jinsheng Zheng, Yi Shen, Lesheng Lin, Jian Li

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Endothelin(ET) axis plays a key role in many tumor progression and metastasis via various mechanisms such as angiogenesis, mediating extracellular matrix degradation and inhibition of apoptosis. However, there is limited information regarding the clinical significance of plasma big ET-1 levels in esophageal cancer patients. Circulating plasma big ET-1 levels were measured in patients with esophageal squamous cell carcinoma(ESCC) to evaluate the value of ET-1 as a biomarker for predicting tumor recurrence and patients survival.

Methods

Preoperative plasma big ET-1 concentrations were measured by an enzyme linked immunosorbent assay(ELISA) in 108 ESCC patients before surgery, and then again at 1,2,3,10 and 30 days after curative radical resection for ESCC. The association between preoperative plasma big ET-1 levels and clinicopathological features, tumor recurrence and patient survival, and their changes following surgery were evaluated.

Results

The preoperative plasma big ET-1 levels in ESCC patients were significantly higher than those in controls. And there was a significant association between plasma big ET-1 levels and disease stage, as well as invasion depth of the tumor and lymph node status. Furthermore, plasma big ET-1 levels decreased significantly after radical resection of the primary tumor and patients with postoperative recurrence had significantly higher plasma big ET-1 levels than that of patients without recurrence. Finally, the survival rate of patients with higher plasma big ET-1 concentrations (>4.3 pg/ml) was significantly lower than that of patients with lower level (≤ 4.3 pg/ml). Multivariate regression analysis showed that plasma big ET-1 level is an independent prognostic factor for survival in patients with ESCC.

Conclusion

Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for choice of multimodality therapy in ESCC patients.
Appendix
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Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRefPubMed
2.
Portale G, Hagen JA, Peters JH, Chan LS, DeMeester SR, Gandamihardja TA, DeMeester TR: Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients. J Am Coll Surg. 2006, 202: 588-596. 10.1016/j.jamcollsurg.2005.12.022.CrossRefPubMed
3.
Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med. 2003, 349: 2241-2252. 10.1056/NEJMra035010.CrossRefPubMed
4.
Shiozaki H, Doki Y, Kawanishi K, Shamma A, Yano M, Inoue M, Monden M: Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers. Surgery. 2000, 127: 552-561. 10.1067/msy.2000.105028.CrossRefPubMed
5.
Korst RJ, Kansler AL, Port JL, Lee PC, Kerem Y, Altorki NK: Downstaging of T or N predicts long-term survival after preoperative chemotherapy and radical resection for esophageal carcinoma. Ann Thorac Surg. 2006, 82: 480-484. 10.1016/j.athoracsur.2006.03.072.CrossRefPubMed
6.
Tajima T, Mukai M, Sato S, Ninomiya H, Wakui K, Komatsu N, Tsuchiya K, Nakasaki H, Makuuchi H: Predicting recurrence and metastasis of primary esophageal cancer with or without lymph node metastasis. Oncol Rep. 2006, 15: 809-814.PubMed
7.
Hosch SB, Stoecklein NH, Pichlmeier U, Rehders A, Scheunemann P, Niendorf A, Knoefel WT, Izbicki JR: Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol. 2001, 19: 1970-1975.PubMed
8.
Schneider PM, Baldus SE, Metzger R, Kocher M, Bongartz R, Bollschweiler E, Schaefer H, Thiele J, Dienes HP, Mueller RP, Hoelscher AH: Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer: implications for response classification. Ann Surg. 2005, 242: 684-92. 10.1097/01.sla.0000186170.38348.7b.CrossRefPubMedPubMedCentral
9.
Mai HQ, Zeng ZY, Zhang CQ, Feng KT, Guo X, Mo HY, Deng MQ, Min HQ, Hong MH: Elevated Plasma Big ET-1 Is Associated with Distant Failure in Patients with Advanced-Stage Nasopharyngeal Carcinoma. Cancer. 2006, 106: 1548-1553. 10.1002/cncr.21790.CrossRefPubMed
10.
Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T: The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA. 1989, 86: 2863-2867. 10.1073/pnas.86.8.2863.CrossRefPubMedPubMedCentral
11.
Ahmed SI, Thompson J, Coulson JM, Woll PJ: Studies on the expression of endothelin, its receptor subtypes, and converting enzymes in lung cancer and in human bronchial epithelium. Am J Respir Cell Mol Biol. 2000, 22: 422-431.CrossRefPubMed
12.
Everson NW, Elahi MM: Prognosis of Colorectal Cancer Patients with Elevated Endothelin-1 Concentrations. Asian J Surg. 2004, 27: 4-9.CrossRefPubMed
13.
Hemsen A, Ahlborg G, Ottosson-Seeberger A, Lundberg JM: Metabolism of big endothelin-1 (1–38) and (22–38) in the human circulation in relation to production of endothelin-1 (1–21). RegulPept. 1995, 55: M287-297.
14.
Wulfing P, Kersting C, Tio J, Fischer RJ, Wulfing C, Poremba C, Diallo R, Bocker W, Kiesel L: Endothelin-1-, Endothelin-A-, and Endothelin-B-Receptor Expression Is Correlated with Vascular Endothelial Growth Factor Expression and Angiogenesis in Breast Cancer. Clin Cancer Res. 2004, 10: 2393-2400. 10.1158/1078-0432.CCR-03-0115.CrossRefPubMed
15.
Spinella F, Rosano L, Di Castro V, Natali PG, Bagnato A: Endothelin-1 induces vascular endothelial growth factor by increasing hypoxia-inducible factor 1α in ovarian cancer cells. J Biol Chem. 2002, 277: 27850-27855. 10.1074/jbc.M202421200.CrossRefPubMed
16.
Salani D, Taraboletti G, Rosano L, Di Castro V, Borsotti P, Giavazzi R, Bagnato A: Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Am J Pathol. 2000, 157: 1703-1711.CrossRefPubMedPubMedCentral
17.
Del Bufalo D, Di Castro V, Biroccio A, Varmi M, Salani D, Rosano L, Triciuoglio D, Spinella F, Bagnato A: Endothelin-1 protects ovarian carcinoma cells against paclitaxel-induced apoptosis: requirement for Akt activation. Mol Pharmacol. 2002, 61: 524-532. 10.1124/mol.61.3.524.CrossRefPubMed
18.
Rosano L, Varmi M, Salani D, Di Castro V, Spinella F, Natali PG, Bagnato A: Endothelin-1 induces tumor proteinase activation and invasiveness of ovarian carcinoma cells. Cancer Res. 2001, 61: 8340-8346.PubMed
19.
Jiao WJ, Xu J, Pan H, Wang TY, Shen Y: Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B. World J Gastroenterol. 2007, 13: 4002-4005.CrossRefPubMedPubMedCentral
20.
Sobin LH, Wittekind C: TNM Classification of Malignant Tumours. New York, Wiley-Liss, 5
21.
Boldrini L, Gisfredi S, Ursino S, Faviana P, Lucchi M, Melfi F, Mussi A, Basolo F, Fontanini G: Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma. Eur J Cancer. 2005, 41: 2828-2835. 10.1016/j.ejca.2005.08.030.CrossRefPubMed
22.
Donckier JE, Michel L, Van Beneden R, Delos M, Havaux X: Increased expression of endothelin-1 and its mitogenic receptor ETA in human papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2003, 59: 354-360. 10.1046/j.1365-2265.2003.01855.x.CrossRef
23.
Venuti A, Salani D, Manni V, Poggiali F, Bagnato A: Expression of endothelin 1 and endothelin A receptor in HPV-associated cervical carcinoma: new potential targets for anticancer therapy. FASEB J. 2000, 14: 2277-2283. 10.1096/fj.00-0024com.CrossRefPubMed
24.
Wulfing P, Tio J, Kersting C, Sonntag B, Buerger H, Wulfing C, Euler U, Boecker W, Tulusan AH, Kiesel L: Expression of endothelin-A-receptor predicts unfavourable response to neoadjuvant chemotherapy in locally advanced breast cancer. Br J Cancer. 2004, 91: 434-440. 10.1038/sj.bjc.6601889.CrossRefPubMedPubMedCentral
25.
Kawanabe Y, Hashimoto N, Masaki T: Effects of extracellular Ca2+ influx on endothelin-1-induced intracellular mitogenic cascades in C6 glioma cells. Eur J Pharmacol. 2002, 435: 119-123. 10.1016/S0014-2999(01)01492-3.CrossRefPubMed
26.
Kawanabe Y, Hashimoto N, Masaki T: B103 neuroblastoma cells predominantly express endothelin ET(B) receptor; effects of extracellular Ca(2+) influx on endothelin-1-induced mitogenesis. Eur J Pharmacol. 2001, 425: 173-179. 10.1016/S0014-2999(01)01150-5.CrossRefPubMed
27.
28.
Duan J, Dai S, Fang CX, Sun R, Shavali S, Sharma SK, Ebadi M, Ren J: Phytoestrogen alpha-zearalanol antagonizes homocysteine-induced imbalance of nitric oxide/endothelin-1 and apoptosis in human umbilical vein endothelial cells. Cell Biochem Biophys. 2006, 45: 137-145. 10.1385/CBB:45:2:137.CrossRefPubMed
29.
Bhargava S, Stummeyer T, Hotz B, Hines OJ, Reber HA, Buhr HJ, Hotz HG: Selective inhibition of endothelin receptor A as an anti-angiogenic and anti-proliferative strategy for human pancreatic cancer. J Gastrointest Surg. 2005, 9: 703-709. 10.1016/j.gassur.2004.11.007.CrossRefPubMed
30.
Medinger M, Adler CP, Schmidt-Gersbach C, Soltau J, Droll A, Unger C, Drevs J: Angiogenesis and the ET-1/ETA receptor system: immunohistochemical expression analysis in bone metastases from patients with different primary tumors. Angiogenesis. 2003, 6: 225-231. 10.1023/B:AGEN.0000021395.43438.44.CrossRefPubMed
31.
Knowles J, Loizidou M, Taylor I: Endothelin-1 and angiogenesis in cancer. Curr Vasc Pharmacol. 2005, 3: 309-314. 10.2174/157016105774329462.CrossRefPubMed
32.
Felx M, Guyot MC, Isler M, Turcotte RE, Doyon J, Khatib AM, Leclerc S, Moreau A, Moldovan F: Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the transcription factor NF-kappaB in human osteosarcoma. Clin Sci(Lond). 2006, 110: 645-654. 10.1042/CS20050286.CrossRef
33.
Rosano L, Spinella F, Di Castro V, NIcotra MR, Dedhar S, de Herreros AG, Natali PG, Bagnato A: Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells. Cancer Res. 2005, 65: 11649-11657. 10.1158/0008-5472.CAN-05-2123.CrossRefPubMed
34.
Hagemann T, Binder C, Binder L, Pukrop T, Trumper L, Grimshaw MJ: Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells. DNA Cell Biol. 2005, 24: 766-776. 10.1089/dna.2005.24.766.CrossRefPubMed
35.
Ishibashi Y, Hanyu N, Nakada K, Suzuki Y, Yamamoto T, Takahashi T, Kawasaki N, Kawakami M, Matsushima M, Urashima M: Endothelin protein expression as a significant prognostic factor in oesophageal squamous cell carcinoma. Eur J Cancer. 2003, 39: 1409-1415. 10.1016/S0959-8049(03)00318-6.CrossRefPubMed
36.
Onizuka M, Miyauchi T, Mitsui K, Suzuki N, Masaki T, Goto K, Hori M: Endothelin-1 mediates regional blood flow during and after pulmonary operations. J Thorac Cardiovasc Surg. 1992, 104: 1696-1701.PubMed
37.
Battistini B, D'Orleans-Juste P, Sirois P: Endothelins: circulating plasma levels and presence in other biologic fluids. Lab Invest. 1993, 68: 600-628.PubMed
38.
Shirakami G, Magaribuchi T, shingu K, Saito Y, O'higashi T, Nakao K, Mori K: Effects of anesthesia and surgery on plasma endothelin levels. Anesth Analg. 1995, 80: 449-453. 10.1097/00000539-199503000-00003.PubMed
39.
Itoh K, Goseki N, Endo M, Hirata Y, Marumo F: Intraoperative hemorrhage affects endothelin-1 concentrations. Am J Gastroenterol. 1991, 86: 118-119.PubMed
40.
Ferrari-Bravo A, Franciosi C, Lissoni P, Fumagalli L, Uggeri F: Effects of oncological surgery on endothelin-1 secretion in patients with operable gastric cancer. Int J Biol Markers. 2000, 15: 56-57.PubMed
41.
Teng XJ, Shen ZX, Xiang JJ, Shen L, Yuan L, Guo J, Wang XL: Pre- and post-operative plasma big endothelin-1 levels in patients with gastric carcinoma undergoing radical gastrectomy. Anticancer Res. 2006, 26: 2503-2507.PubMed
42.
Nishimaki T, Shimoji H, Sunagawa H: Recent Changes and the Future Roles of Esophageal Cancer Surgery. Ann Thorac Cardiovasc Surg. 2004, 10: 324-332.PubMed
Metadata
Title
Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma
Authors
Wenjie Jiao
Jing Xu
Jinsheng Zheng
Yi Shen
Lesheng Lin
Jian Li
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-334

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