The
aims of this study were to examine prognostic significance of pigment epithelium-derived
factor (PEDF) in patients with stage IA-IIIB non-small cell lung cancer (NSCLC).
Using immunohistochemistry and multivariate analysis, we set out to investigate whether PEDF expression
could provide prognostic information in NSCLC in a cohort of 69 patients who
had undergone radical resection for NSCLC. The correlation between PEDF and the
clinical pathological features of stage I-III NSCLC after radical surgery were
analyzedas well as
influence on long term survival. No correlation between PEDF intensity, PEDF
area or PEDF area index and clinicopathologic
parameters was seen. PEDF values showed a slight correlation to the tumor
stage. There was a significant negative correlation (T=-0.288, p=0.002)
between pathologic T-stage and median PEDF area and vice versa a positive
correlation (T=0.227, p=0.016) with median PEDF intensity. We could not
detect any correlation between PEDF and long term survival. For PEDF analysis, there was only a slight correlation between expression
and T-stage of the tumor.
References
[1]
El Masri, J., Ren, S. and Zhang, J. (2016) Getting Familiar with the Forthcoming Eighth Edition of TNM Classification of Lung Cancer: From the T to N and M Descriptors. Annals of Translational Medicine, 4, 67.
[2]
Hanahan, D. and Folkman, J. (1996) Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis. Cell, 86, 353-364.
http://dx.doi.org/10.1016/S0092-8674(00)80108-7
[3]
Folkman, J. (1989) What Is the Evidence That Tumors Are Angiogenesis Dependent? Journal of the National Cancer Institute, 82, 4-6.
[4]
Bodnar, R.J. (2015) Chemokine Regulation of Angiogenesis during Wound Healing. Advances in Wound Care (New Rochelle), 4, 641-650.
http://dx.doi.org/10.1089/wound.2014.0594
[5]
Pao, W. and Girard, N. (2011) New Driver Mutations in Non-Small-Cell Lung Cancer. The Lancet Oncology, 12, 175-180. http://dx.doi.org/10.1016/S1470-2045(10)70087-5
[6]
Fu, L., Shi, K., Wang, J., Chen, W., Shi, D., Tian, Y., Guo, W., Yu, W., Xiao, X., Kang, T., Wang, S., Huang, W. and Deng, W. (2014) TFAP2B Overexpression Contributes to Tumor Growth and a Poor Prognosis of Human Lung Adenocarcinoma through Modulation of ERK and VEGF/PEDF Signaling. Molecular Cancer, 13, 89.
http://dx.doi.org/10.1186/1476-4598-13-89
[7]
Villaruz, L.C. and Socinski, M.A. (2015) The Role of Anti-Angiogenesis in Non-Small-Cell Lung Cancer: An Update. Current Oncology Reports, 17, 26.
http://dx.doi.org/10.1007/s11912-015-0448-y
[8]
Pignolo, R.J., Cristofalo, V.J. and Rotenberg, M.O. (1993) Senescent WI-38 Cells Fail to Express EPC-1, a Gene Induced in Young Cells upon Entry into the G0 State. The Journal of Biological Chemistry, 268, 8949-8957.
[9]
Pignolo, R.J., Rotenberg, M.O. and Cristofalo, V.J. (1995) Analysis of EPC-1 Growth State-Dependent Expression, Specificity, and Conservation of Related Sequences. Journal of Cellular Physiology, 162, 110-118. http://dx.doi.org/10.1002/jcp.1041620113
[10]
Dawson, D.W., Volpert, O.V., Gillis, P., Crawford, S.E., Xu, H., Benedict, W. and Bouck, N.P. (1999) Pigment Epithelium-Derived Factor: A Potent Inhibitor of Angiogenesis. Science, 285, 245-248. http://dx.doi.org/10.1126/science.285.5425.245
[11]
Steele, F.R., Chader, G.J., Johnson, L.V. and Tombran-Tink, J. (1993) Pigment Epithelium-Derived Factor: Neurotrophic Activity and Identification as a Member of the Serine Protease Inhibitor Gene Family. Proceedings of the National Academy of Sciences of the United States of America, 90, 1526-1530. http://dx.doi.org/10.1073/pnas.90.4.1526
[12]
Broadhead, M.L., Dass, C.R. and Choong, P.F. (2009) In Vitro and in Vivo Biological Activity of PEDF against a Range of Tumors. Expert Opinion on Therapeutic Targets, 13, 1429-1438. http://dx.doi.org/10.1517/14728220903307475
[13]
Li, L., Yao, Y.C., Fang, S.H., Ma, C.Q., Cen, Y., Xu, Z.M., Dai, Z.Y., Li, C., Li, S., Zhang, T., Hong, H.H., Qi, W.W., Zhou, T., Li, C.Y., Yang, X. and Gao, G.Q. (2014) Pigment Epithelial-Derived Factor (PEDF)-Triggered Lung Cancer Cell Apoptosis Relies on p53 Protein-Driven Fas Ligand (Fas-L) Up-Regulation and Fas Protein Cell Surface Translocation. The Journal of Biological Chemistry, 289, 30785-30799.
http://dx.doi.org/10.1074/jbc.M114.590000
[14]
Hoshina, D., Abe, R., Yamagishi, S.I. and Shimizu, H. (2010) The Role of PEDF in Tumor Growth and Metastasis. Current Molecular Medicine, 10, 292-295.
http://dx.doi.org/10.2174/156652410791065327
[15]
Zhou, D., Zhang, M., Xu, P., Yu, Y., Ye, G., Zhang, L. and Wu, A. (2016) Expression of Pigment Epithelium-Derived Factor Is Associated with a Good Prognosis and Is Correlated with Epithelial-Mesenchymal Transition-Related Genes in Infiltrating Ductal Breast Carcinoma. Oncology Letters, 11, 116-124.
[16]
Hillen, F. and Griffioen, A.W. (2007) Tumour Vascularization: Sprouting Angiogenesis and Beyond. Cancer and Metastasis Reviews, 26, 489-502.
http://dx.doi.org/10.1007/s10555-007-9094-7
[17]
Zhou, D., Cheng, S.Q., Ji, H.F., Wang, J.S., Xu, H.T., Zhang, G.Q. and Pang, D. (2010) Evaluation of Protein Pigment Epithelium-Derived Factor (PEDF) and Microvessel Density (MVD) as Prognostic Indicators in Breast Cancer. Journal of Cancer Research and Clinical Oncology, 136, 1719-1727. http://dx.doi.org/10.1007/s00432-010-0830-y
[18]
Massuti, B., Sanchez, J.M., Hernando-Trancho, F., Karachaliou, N. and Rosell, R. (2013) Are We Ready to Use Biomarkers for Staging, Prognosis and Treatment Selection in Early-Stage Non-Small-Cell Lung Cancer? Translational Lung Cancer Research, 2, 208-221.
[19]
Chandolu, V. and Dass, C.R. (2012) Cell and Molecular Biology Underpinning the Effects of PEDF on Cancers in General and Osteosarcoma in Particular. Journal of Biomedicine and Biotechnology, 2012, Article ID: 740295. http://dx.doi.org/10.1155/2012/740295
[20]
Shi, H.S., Yang, L.P., Wei, W., Su, X.Q., Li, X.P., Li, M., Luo, S.T., Zhang, H.L., Lu, L., Mao, Y.Q., Kan, B. and Yang, L. (2013) Systemically Administered Liposome-Encapsulated Ad-PEDF Potentiates the Anti-Cancer Effects in Mouse Lung Metastasis Melanoma. Journal of Translational Medicine, 11, 86. http://dx.doi.org/10.1186/1479-5876-11-86
[21]
Hase, R., Miyamoto, M., Uehara, H., Kadoya, M., Ebihara, Y., Murakami, Y., Takahashi, R., Mega, S., Li, L., Shichinohe, T., Kawarda, Y. and Kondo, S. (2005) Pigment Epithelium-Derived Factor Gene Therapy Inhibits Human Pancreatic Cancer in Mice. Clinical Cancer Research, 11, 8737-8744. http://dx.doi.org/10.1158/1078-0432.CCR-05-1323
[22]
Uehara, H., Miyamoto, M., Kato, K., Ebihara, Y., Kaneko, H., Hashimoto, H., Murakami, Y., Hase, R., Takahashi, R., Mega, S., Shichinohe, T., Kawarady, Y., Itoh, T., Okushiba, S., Kondo, S. and Katoh, H. (2004) Expression of Pigment Epithelium-Derived Factor Decreases Liver Metastasis and Correlates with Favorable Prognosis for Patients with Ductal Pancreatic Adenocarcinoma. Cancer Research, 64, 3533-3537.
http://dx.doi.org/10.1158/0008-5472.CAN-03-3725
