0%) were positively check details stained, and 8 (19.0%) were negatively stained. www.selleckchem.com/products/KU-55933.html We also found a significant decrease of SMAD4 expression in glioma compared with normal brain tissues (P < 0.001).

Figure 1 Immunohistochemical staining of SMAD4 protein in tumor cells of GBM (A) and astrocytoma (B) (Original magnification ×400). Staining for this antigen is described in Materials and Methods. Positive staining of SMAD4 is seen in the cytoplasm and/or nuclei of tumors cells and is more abundant in the low- (B) than the high-grade (A) tumors. Intensively positive expression of SMAD4 (C) was observed in normal brain tissues. In addition, SMAD4 expression was not significantly affected by the gender and age (both P > 0.05) of the patients. In contrast, the SMAD4 expression was the closely correlated

with WHO grade Capmatinib concentration (Table 1; P = 0.008), as well as Karnofsky performance Status (KPS) (Table 1; P < 0.001). Table 1 SMAD4 expression in human glioma tissues with different clinical-pathological features Clinicopathological features No. of cases SMAD4 (n) P     - + ++ +++   WHO grade   114 60 51 27   I 53 12 16 13 12 0.008 II 60 17 21 15 7   III 62 34 12 11 5   IV 77 51 11 12 3   Age             <55 152 65 39 31 17 NS ≥55 100 49 21 20 10   Gender             Male 138 57 36 30 15 NS Female 114 57 24 21 12   KPS             <80 135 81 25 21 8 <0.001 ≥80 117 33 35 30 19   Moreover, we reviewed clinical information of these SMAD4-positive these or -negative glioma patients. During the follow-up period, 197 of the 252 glioma patients (78.2%) had died (108 from the SMAD4-negative group and 142 from the SMAD4-positive group). As determined by the log-rank

test, the survival rate of patients without SMAD4 staining was lower than those showing SMAD4 positive staining (P < 0.001; Figure 2A). The median survival time of patients with strong positive (+++) expression of SMAD4 could not be estimated by statistical analysis because all patients survived better than the overall median level, and those patients with moderate positive (++), weak positive (+) and negative expression of SMAD4 were 22.8 ± 1.3 months, 13.2 ± 1.6 months and 8.0 ± 0.5 months (log-rank test: P < 0.001). Figure 2 Postoperative survival curves for patterns of patients with glioma and SMAD4 expression. (A) Kaplan-Meier postoperative survival curve for patterns of patients with glioma and SMAD4 expression. Unadjusted RR of SMAD4-negative (-), weak positive (+), moderate positive (++) and strong positive (+++) groups were 1.0, 0.4, 0.08 and 0.02, respectively (P < 0.001). (B) Cox proportional hazards model after adjusting for age, gender and grade. SMAD4 might be an independent predictor of survival, without consideration of age, gender or grade. Adjusted RR of SMAD4-negative (-), weak positive (+), moderate positive (++) and strong positive (+++) groups were 1.0, 0.4, 0.2 and 0.04, respectively (P < 0.001).