Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages

Abstract

Objective: High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Material and Methods: Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. Results: HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). Conclusion: These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer. Turkish Anahtar Kelimeler: Mide kanseri, lipid peroksidasyon, TGF-β1 Amaç: Yüksek TGF-β1 seviyeleri ve gelişmiş TGF-β1 reseptör sinyalizasyonu mide kanseri patolojisi ile ilişkilidir. Bu etki oksidatif stres ve lipid peroksidasyon ürünleri tarafından oluşmaktadır. Bu çalışmada amaç, mide kanserli hastalarda TGF-β1 ve lipit peroksidasyon ürün düzeylerini ve bu ürünlerin patolojik evre ile korelasyonunu araştırmaktı. Materyal ve Metod: Mide kanserli 50 hasta ve sağlıklı 18 kişinin serumunda lipid peroksidasyon ürün ve TGF-β1 seviyelerine bakıldı. Sonuçlar: T2, T3 ve T4 tümörlü hastaların HNE ve TGF-β1 seviyeleri hem T1 hem de sağlıklı kişilere göre anlamlı derecede yüksek bulundu (p<0.001). TGF-β1 seviyeleri patolojik evre ile korele idi (r=0.702, p<0.05). Sonuç: Bu markırların üretimi, tümör anjiyogenezisine katkıda bulunabilir ve mide kanseri prognozunun belirlenmesinde yardımcı olabilir.

Keywords

• Gastric cancer, lipid peroxidation, TGF-β1

Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages

Öz

Kaynakça

1. Akgül H, Ünal E, Demirci S, Kocaoğlu H, Bayar S. Mide Kanser- inde D2-3 Diseksiyon Deneyimimiz. T Klin Cerrahi 1999;4:211-5.
2. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric Adenocarcinoma: review and considerations for future directions. Ann Surg 2005;241:27-39.
3. Green D, Ponce de Leon S, Leon-Rodriguez E, Sosa-Sanchez R. Adenocarcinoma of the stomach: univariate and multivari- ate analysis of factors associated with survival. Am J Clin Oncol 2002;25:84-9. [CrossRef]
4. Roberts AB, Sporn MB. Physiological actions and clinical appli- cations of transforming growth factor-beta (TGF-beta). Growth Factors 1993;8:1-9. [CrossRef]
5. Massagué J. TGF-beta signaling: receptors, transducers, and Mad proteins. Cell 1996;85:947-50. [CrossRef]
6. Geiser AG, Busam KJ, Kim SJ, Lafyatis R, O’Reilly MA, Web- bink R, et al. Regulation of the transforming growth factor -beta1 and -beta3 promoters by transcription factor Sp1. Gene 1993;129:223-8. [CrossRef]
7. Grande JP. Role of the transforming growth factor-beta in tissue injury and repair. Proc Soc Exp Biol Med 1997;214:27-40.
8. Massagué J, Cheifetz S, Laiho M, Ralph DA, Weis FM, Zentella A. Transforming growth factor-beta. Cancer Surv 1992;12:81-103.

9. Winesett MP, Ramsey GW, Barnard JA. Type II TGF (beta) recep- tor expression in intestinal cell lines and in the intestinal tract. Carcinogenesis 1996;17:989-95. [CrossRef]
10. Landström M, Eklov S, Colosetti P, Nilsson S, Damber JE, Bergh A, et al. Estrogen induces apoptosis in a rat prostatic adenocar- cinoma: association with an increased expression of TGF-beta 1 and its type-I and type-II receptors. Int J Cancer 1996;67:573-9. [CrossRef]
11. Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, et al. Expression of transforming growth factor beta type II recep- tor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem 1994;269:26449-55.
12. Kim WS, Park C, Jung YS, Kim HS, Han J, Park CH, et al. Re- duced transforming growth factor-beta type II receptor (TGF- beta RII) expression in adenocarcinoma of the lung. Anticancer Res 1999;19:301-6.
13. Leonarduzzi G, Scavazza A, Biasi F, Chiarpotto E, Camandola S, Vogel S, et al. The lipid peroxidation end product 4-hydroxy-2,3- nonenal up-regulates transforming growth factor beta1 express- sion in the macrophage lineage: a link between oxidative injury and fibrosclerosis. FASEB J 1997;11:851-7.
14. Dianzani MU. Lipid peroxidation and cancer. Crit Rev Oncol He- matol 1993;15:125-47. [CrossRef]
15. Ellis FH Jr, Heatley GJ, Balogh K. Proposal for improved staging criteria for carcinoma of the esophagus and cardia. Eur J Cardio- thorac Surg 1997;12:361-4. [CrossRef]
16. Carini R, Mazzanti M, Biasi F. Fluorescent aldehyde-protein ad- ducts in the blood serum of healthy alcoholics. Alcohol Toxicity and Free Radical Mechanisms Oxford: Pergamon Press, 1988; 664.
17. Tsuchida M, Miura T, Mizutani K, Aibara K. Fluorescence sub- stances in mouse and human sera as a parameter of in vivo lipid 275
18. ; 29: 273-6 Tüzün et al.
19. TGF- β1 Levels in Gastric Cancer