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. 2008 May 16;22(3):164–171. doi: 10.1002/jcla.20236

Elevated serum level and gene polymorphisms of TGF‐β1 in gastric cancer

Xue Li 1,†, Zhi‐Chao Yue 1,‡, Yun‐Yan Zhang 2, Jing Bai 1, Xiang‐ning Meng 1, Jing‐Shu Geng 2, Song‐Bin Fu 1,✉
PMCID: PMC6649059  PMID: 18484655

Abstract

Transforming growth factor (TGF)‐β1, as a candidate tumor marker, is currently of interest. In this study, serum TGF‐β1 levels in gastric cancer (GC) patients and healthy volunteers were measured using enzyme‐linked immunosorbent assay (ELISA). In addition, single nucleotide polymorphisms (SNPs) of the TGF‐β1 gene at codon 10 and codon 25 were identified by means of amplification refractory mutation system–polymerase chain reaction (ARMS‐PCR) and sequence analysis. Our results indicated that serum concentrations of TGF‐β1 in GC patients were significantly higher than those in the control, and positively correlated with tumor mass, invasion, metastasis, and clinical stage. The serum TGF‐β1 levels of patients recovering from radical resection were markedly lower than those before surgery. Meanwhile, no deoxyribonucleic acid (DNA) sequence variation at codon 25 of the TGF‐β1 gene was found and a TGF‐β1 gene polymorphism at codon 10 did not show obvious correlations with either TGF‐β1 expression or clinicopathological parameters of GC. Our evidence suggested that serum concentration of TGF‐β1 might be a novel tumor marker for GC and the polymorphisms of TGF‐β1 gene did not play a role as a determinant of serum TGF‐β1 concentration or as a genetic risk factor in the gastric carcinogenesis and progression. J. Clin. Lab. Anal. 22:164–171, 2008. © 2008 Wiley‐Liss, Inc.

Keywords: transforming growth factor‐beta 1, SNPs, ARMS‐PCR, ELISA

REFERENCES

  • 1. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001;2:533–543. [DOI] [PubMed] [Google Scholar]
  • 2. Narai S, Watanabe M, Hasegawa H, et al. Significance of transforming growth factor beta1 as a new tumor marker for colorectal cancer. Int J Cancer 2002;97:508–511. [DOI] [PubMed] [Google Scholar]
  • 3. Shirai Y, Kawata S, Tamura S, et al. Plasma transforming growth factor‐beta 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases. Cancer 1994;73:2275–2279. [DOI] [PubMed] [Google Scholar]
  • 4. Todaro GJ, De Larco JE. Growth factors produced by sarcoma virus‐transformed cells. Cancer Res 1978;38(Pt 2):4147–4154. [PubMed] [Google Scholar]
  • 5. Lyons RM, Gentry LE, Purchio AF, Moses HL. Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol 1990;110:1361–1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Lyons RM, Keski‐Oja J, Moses HL. Proteolytic activation of latent transforming growth factor‐beta from fibroblast‐conditioned medium. J Cell Biol 1988;106:1659–1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Oklu R, Hesketh R. The latent transforming growth factor beta binding protein (LTBP) family. Biochem J 2000;352(Pt 3):601–610. [PMC free article] [PubMed] [Google Scholar]
  • 8. Massague J, Wotton D. Transcriptional control by the TGF‐beta/Smad signaling system. EMBO J 2000;19:1745–1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Rooke HM, Crosier KE. The smad proteins and TGFbeta signalling: uncovering a pathway critical in cancer. Pathology 2001;33:73–84. [PubMed] [Google Scholar]
  • 10. Kang SH, Bang YJ, Im YH, et al. Transcriptional repression of the transforming growth factor‐beta type I receptor gene by DNA methylation results in the development of TGF‐beta resistance in human gastric cancer. Oncogene 1999;18:7280–7286. [DOI] [PubMed] [Google Scholar]
  • 11. Yang HK, Kang SH, Kim YS, Won K, Bang YJ, Kim SJ. Truncation of the TGF‐beta type II receptor gene results in insensitivity to TGF‐beta in human gastric cancer cells. Oncogene 1999. 18:2213–2219. [DOI] [PubMed] [Google Scholar]
  • 12. Niki M, Okajima K, Isozaki H, et al. [Measurement of the plasma transforming growth factor‐beta 1 (TGF‐beta 1) level in patients of gastric carcinoma–compared with the serum IAP level and the lymphocyte subsets (CD3, CD4, CD8)]. Nippon Shokakibyo Gakkai Zasshi 1996;93:303–311 [Japanese]. [PubMed] [Google Scholar]
  • 13. Saito H, Tsujitani S, Oka S, et al. An elevated serum level of transforming growth factor‐beta 1 (TGF‐beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res 2000;20:4489–4493. [PubMed] [Google Scholar]
  • 14. Ivanovic V, Melman A, Davis‐Joseph B, Valcic M, Geliebter J. Elevated plasma levels of TGF‐beta 1 in patients with invasive prostate cancer. Nat Med 1995;1:282–284. [DOI] [PubMed] [Google Scholar]
  • 15. Sacco R, Leuci D, Tortorella C, et al. Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma. Cytokine 2000;12:811–814. [DOI] [PubMed] [Google Scholar]
  • 16. Shariat SF, Shalev M, Menesses‐Diaz A, et al. Preoperative plasma levels of transforming growth factor beta(1) (TGF‐beta(1)) strongly predict progression in patients undergoing radical prostatectomy. J Clin Oncol 2001;19:2856–2864. [DOI] [PubMed] [Google Scholar]
  • 17. Sheen‐Chen SM, Chen HS, Sheen CW, Eng HL, Chen WJ. Serum levels of transforming growth factor beta1 in patients with breast cancer. Arch Surg 2001;136:937–940. [DOI] [PubMed] [Google Scholar]
  • 18. Lin Y, Kikuchi S, Obata Y, Yagyu K. Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol 2006;21:432–437. [DOI] [PubMed] [Google Scholar]
  • 19. Maehara Y, Kakeji Y, Kabashima A, et al. Role of transforming growth factor‐beta 1 in invasion and metastasis in gastric carcinoma. J Clin Oncol 1999;17:607–614. [DOI] [PubMed] [Google Scholar]
  • 20. Watanabe Y, Kinoshita A, Yamada T, et al. A catalog of 106 single‐nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor‐beta1 (TGF‐beta1) and its signaling pathway. J Hum Genet 2002;47:478–483. [DOI] [PubMed] [Google Scholar]
  • 21. Arosio B, Bergamaschini L, Galimberti L, et al. +10 T/C polymorphisms in the gene of transforming growth factor‐beta1 are associated with neurodegeneration and its clinical evolution. Mech Ageing Dev 2007;128:553–557. [DOI] [PubMed] [Google Scholar]
  • 22. Li Z, Habuchi T, Tsuchiya N, et al. Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor‐beta 1 gene polymorphism at codon10. Carcinogenesis 2004;25:237–240. [DOI] [PubMed] [Google Scholar]
  • 23. Pereira FA, Pinheiro da Silva NN, Rodart IF, Carmo TM, Lemaire DC, Reis MG. Association of TGF‐beta1 codon 25 (G915C) polymorphism with hepatitis C virus infection. J Med Virol 2008;80:58–64. [DOI] [PubMed] [Google Scholar]
  • 24. Shu XO, Gao YT, Cai Q, et al. Genetic polymorphisms in the TGF‐beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study. Cancer Res 2004;64:836–839. [DOI] [PubMed] [Google Scholar]
  • 25. Langenskiold M, Holmdahl L, Falk P, Angenete E, Ivarsson ML. Increased TGF‐Beta1 protein expression in patients with advanced colorectal cancer. J Surg Oncol 2008;97:409–415. [DOI] [PubMed] [Google Scholar]
  • 26. Zhou Q, Dong Wang L, Du F, et al. Changes of TGFbeta1 and TGFbetaRII expression in esophageal precancerous and cancerous lesions: a study of a high‐risk population in Henan, northern China. Dis Esophagus 2002;15:74–79. [DOI] [PubMed] [Google Scholar]
  • 27. Newton CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989;17:2503–2516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Gonzalez‐Zuloeta Ladd AM, Arias‐Vasquez A, Siemes C, et al. Transforming‐growth factor beta1 Leu10Pro polymorphism and breast cancer morbidity. Eur J Cancer 2007;43:371–374. [DOI] [PubMed] [Google Scholar]
  • 29. Yamada Y. Association of polymorphisms of the transforming growth factor‐beta1 gene with genetic susceptibility to osteoporosis. Pharmacogenetics 2001;11:765–771. [DOI] [PubMed] [Google Scholar]
  • 30. Awad MR, El‐Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV. Genotypic variation in the transforming growth factor‐beta1 gene: association with transforming growth factor‐beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation 1998;66:1014–1020. [DOI] [PubMed] [Google Scholar]
  • 31. Basturk B, Yavascaoglu I, Vuruskan H, Goral G, Oktay B, Oral HB. Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma. Cytokine 2005;30:41–45. [DOI] [PubMed] [Google Scholar]
  • 32. Verner K, Schatz G. Protein translocation across membranes. Science 1988;241:1307–1313. [DOI] [PubMed] [Google Scholar]
  • 33. Dunning AM, Ellis PD, McBride S, et al. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res 2003;63:2610–2615. [PubMed] [Google Scholar]
  • 34. Hinke V, Seck T, Clanget C, Scheidt‐Nave C, Ziegler R, Pfeilschifter J. Association of transforming growth factor‐beta1 (TGFbeta1) T29 –> C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF‐beta1 in a population‐based sample of postmenopausal German women. Calcif Tissue Int 2001;69:315–320. [DOI] [PubMed] [Google Scholar]
  • 35. Cambien F, Ricard S, Troesch A, et al. Polymorphisms of the transforming growth factor‐beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas‐Temoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension 1996;28:881–887. [DOI] [PubMed] [Google Scholar]

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