DOI QR코드

DOI QR Code

TGF-β1 Protein Expression in Non-Small Cell Lung Cancers is Correlated with Prognosis

  • Huang, Ai-Li (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Liu, Shu-Guang (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Qi, Wen-Juan (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Zhao, Yun-Fei (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Li, Yu-Mei (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Lei, Bin (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Sheng, Wen-Jie (Department of Pathology, Nanfang Hospital, Southern Medical University) ;
  • Shen, Hong (Department of Pathology, Nanfang Hospital, Southern Medical University)
  • Published : 2014.10.23

Abstract

To investigate the expression intensity and prognostic significance of TGF-${\beta}1$ protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-${\beta}1$ protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-${\beta}1$ PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-${\beta}1$ protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000,). Multivariate analysis showed that TGF-${\beta}1$ protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p=0.030) were also independent prognostic factors. Thus, TGF-${\beta}1$ protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.

Keywords

NSCLC;transforming growth factor ${\beta}1$;quantitative analysis;prognosis

References

  1. Assoian RK, Komoriya A, Meyers CA, et al (1983). Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem, 258, 7155-60.
  2. Bai X, Shen H, Zhou C, et al (2009). Expression of thyroid transcription factor-l (TTF-1)in lung carcinomas and its correlations with apoptosis and angiogenesis. Clin Oncol Cancer Res, 6, 16-20.
  3. Blobe GC, Schiemann WP, Lodish HF (2000). Role of transforming growth factor beta in human disease. N Engl J Med, 342, 1350-8. https://doi.org/10.1056/NEJM200005043421807
  4. Boyd FT, Massague J (1989). Transforming growth factorbeta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor. J Biol Chem, 264, 2272-8.
  5. Chen XF, Zhang HJ, Wang HB, et al (2012). Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways. Mol Biol Rep, 39, 3549-56. https://doi.org/10.1007/s11033-011-1128-0
  6. Grady WM, Rajput A, Myeroff L, et al (1998). Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. Cancer Res, 58, 3101-4.
  7. Derynck R, Akhurst RJ, Balmain A (2001). TGF-beta signaling in tumor suppression and cancer progression. Nat Genet, 29, 117-29. https://doi.org/10.1038/ng1001-117
  8. Ellermeier J, Wei J, Duewell P, et al (2013). Therapeutic efficacy of bifunctional siRNA combining TGF-beta1 silencing with RIG-I activation in pancreatic cancer. Cancer Res, 73, 1709-20. https://doi.org/10.1158/0008-5472.CAN-11-3850
  9. Furuta K, Misao S, Takahashi K, et al (1999). Gene mutation of transforming growth factor beta1 type II receptor in hepatocellular carcinoma. Int J Cancer, 81, 851-3. https://doi.org/10.1002/(SICI)1097-0215(19990611)81:6<851::AID-IJC2>3.0.CO;2-D
  10. Tripsianis G, Papadopoulou E, Romanidis K, et al (2013). Overall survival and clinicopathological characteristics of patients with breast cancer in relation to the expression pattern of HER-2, IL-6, TNF-${\alpha}$ and TGF-${\alpha}$. Asian Pac J Cancer Prev, 14, 6813-20. https://doi.org/10.7314/APJCP.2013.14.11.6813
  11. Janda E, Lehmann K, Killisch I, et al (2002). Ras and TGF cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol, 156, 299-313. https://doi.org/10.1083/jcb.200109037
  12. Jemal A, Siegel R, Ward E, et al (2007). Cancer statistics, 2007. CA Cancer J Clin, 57, 43-66. https://doi.org/10.3322/canjclin.57.1.43
  13. Jennings MT, Pietenpol JA (1998). The role of transforming growth factor beta in glioma progression. J Neurooncol, 36, 123-40. https://doi.org/10.1023/A:1005863419880
  14. Kasai H, Allen JT, Mason RM, et al (2005). TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir Res, 6, 56. https://doi.org/10.1186/1465-9921-6-56
  15. Kim WS, Park C, Jung YS, et al (1999). Reduced transforming growth factor-beta type II receptor (TGF-beta RII) expression in adenocarcinoma of the lung. Anticancer Res, 19, 301-6.
  16. Markowitz S, Wang J, Myeroff L, et al (1995). Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science, 268, 1336-8. https://doi.org/10.1126/science.7761852
  17. Lei B, Liu S, Qi WJ, et al (2013). PBK/TOPK expression in non-small-cell lung cancer: its correlation and prognostic significance with Ki67 and p53 expression. Histopathology, 63, 696-703.
  18. Luwor RB, Kaye, AH, Zhu HJ (2008). Transforming growth factor-beta (TGF-beta) and brain tumours. J Clin Neurosci, 15, 845-55. https://doi.org/10.1016/j.jocn.2008.01.003
  19. Ma J, Gao H-M, Hua X, et al (2014). Role of TGF-${\beta}1$ in human colorectal cancer and effects after cantharidinate intervention. Asian Pac J Cancer Prev, 15, 4045-8. https://doi.org/10.7314/APJCP.2014.15.9.4045
  20. Rich J, Borton A, Wang X (2001). Transforming growth factorbeta signaling in cancer. Microsc Res Tech, 52, 363-73. https://doi.org/10.1002/1097-0029(20010215)52:4<363::AID-JEMT1021>3.0.CO;2-F
  21. Siegel PM, Massague J (2003). Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer, 3, 807-21. https://doi.org/10.1038/nrc1208
  22. Shen H, Lu Y (1993). Study on quantitative method of immunochemical staining. J Biomed Eng, 10, 281-4.
  23. Shen H (1994). Study on quantitative method of intensity of immunohistochemical staining (II). J Cell Mol Immunol, 10, 33-5.
  24. Shen H (1995). Study on quantitative method of immunochemical staining (III). Chin J Histochem Cytochem, 4, 89-92.
  25. Takanami I, Imamura T, Hashizume T, et al (1994). Transforming growth factor beta 1 as a prognostic factor in pulmonary adenocarcinoma. J Clin Pathol, 47, 1098-100. https://doi.org/10.1136/jcp.47.12.1098
  26. Takanami I, Tanaka F, Hashizume T, et al (1997). Roles of the transforming growth factor beta 1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: results of an immunohistochemical study. J Surg Oncol, 64, 262-7. https://doi.org/10.1002/(SICI)1096-9098(199704)64:4<262::AID-JSO3>3.0.CO;2-7
  27. Xu XY, Lin N, Li YM, et al (2013). Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer. Pathol Res Pract, 209, 345-52. https://doi.org/10.1016/j.prp.2013.02.015
  28. Wan L, Li X, Shen H, et al (2013). Quantitative analysis of EZH2 expression and its correlations with lung cancer patients' clinical pathological characteristics. Clin Transl Oncol, 15, 132-8. https://doi.org/10.1007/s12094-012-0897-9
  29. Wiedmann MW, Caca K (2005). Molecularly targeted therapy for gastrointestinal cancer. Curr Cancer Drug Targets, 5, 171-93. https://doi.org/10.2174/1568009053765771
  30. Xu CC, Wu LM, Sun W, et al (2011). Effects of TGF-beta signaling blockade on human A549 lung adenocarcinoma cell lines. Mol Med Rep, 4, 1007-15.
  31. Xue YJ, Lu Q, Sun ZX (2011). CD147 overexpression is a prognostic factor and a potential therapeutic target in bladder cancer. Med Oncol, 28, 1363-72. https://doi.org/10.1007/s12032-010-9582-4
  32. Yanagisawa K, Uchida K, Nagatake M, et al (2000). Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers. Oncogene, 19, 2305-11. https://doi.org/10.1038/sj.onc.1203591

Cited by

  1. Prognostic Value of Tissue Inhibitor of Metalloproteinase-2 Expression in Patients with Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis vol.10, pp.4, 2015, https://doi.org/10.1371/journal.pone.0124230
  2. Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression vol.35, pp.4, 2016, https://doi.org/10.3892/or.2016.4615
  3. Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-27912-1
  4. Role of natural killer cells in lung cancer vol.144, pp.6, 2018, https://doi.org/10.1007/s00432-018-2635-3