Thus, SMAD4 might be an independent predictor of survival for glioma patients. In our study, which consisted
of a large sample (n = 252), SMAD4 expression was analyzed by immunohistochemistry, real-time PCR and Western blot analysis. Thus, a large sample size, a good methodology and a detailed clinical follow-up in our study make it reliable. In conclusion, our data provides convincing evidence for the first time that the reduced check details expression of SMAD4 at gene and protein levels is correlated with poor outcome in patients with glioma. SMAD4 may play an inhibitive role during the development of glioma and may be a potential prognosis predictor of glioma. References 1. Li X, Wang L, Gu JW, Li B, Liu WP, Wang YG, Zhang X, Zhen HN, Fei Z: Up-regulation of EphA2
and down-regulation of EphrinA1 are associated with the aggressive phenotype and poor prognosis of malignant glioma. Tumour Biol 2010, 31:477–488.PubMedCrossRef 2. Sun B, Chu D, Li W, Chu X, Li Y, Wei D, Li H: Decreased expression of NDRG1 in glioma is related to tumor progression and survival of patients. J Neurooncol 2009, 94:213–219.PubMedCrossRef 3. Ding Z, Wu CJ, Chu GC, Xiao Y, Ho D, Zhang J, Perry SR, Labrot ES, Wu X, Lis R, Hoshida INCB024360 ic50 Y, Hiller D, Hu B, Jiang S, Zheng H, Stegh AH, Scott KL, Signoretti S, Bardeesy N, Wang YA, Hill DE, Golub TR, Stampfer MJ, Wong WH, Loda M, Mucci L, Chin L, DePinho RA: SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature 2011, 470:269–273.PubMedCrossRef 4. Ali NA, McKay MJ, Molloy MP: Proteomics of Smad4 regulated transforming growth factor-beta signalling in colon cancer cells. Mol Biosyst 2010, 6:2332–2338.PubMedCrossRef 5. Papageorgis P, Cheng K, Ozturk S, Gong Y, Lambert AW, Abdolmaleky HM, Zhou JR, Thiagalingam S: Smad4 inactivation promotes malignancy and drug resistance of colon cancer. Cancer Res 2011, 71:998–1008.PubMedCrossRef 6. Sakellariou S, Liakakos T, Ghiconti I, Hadjikokolis Verteporfin clinical trial S, Nakopoulou L, Pavlakis K: Immunohistochemical expression of P15 (INK4B) and SMAD4 in advanced gastric
cancer. Anticancer Res 2008, 28:1079–1083.PubMed 7. Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Eshleman JR, Goggins M, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Cameron JL, Olino K, Schulick R, Winter J, Herman JM, Laheru D, Klein AP, Vogelstein B, Kinzler KW, Velculescu VE, Hruban RH: SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res 2009, 15:4674–4679.PubMedCrossRef 8. Ke Z, Zhang X, Ma L, Wang L: Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non-small cell lung cancer. Hum Pathol 2008, 39:1438–1445.PubMedCrossRef 9. Lv J, Cao XF, Ji L, Zhu B, Wang DD, Tao L, Li SQ: Association of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma.