Of the 67 cases with ATM inhibitor follow-up, 20 cases had over one year survival, and 47 died within one year after surgery, with a mean survival time of 9.6 ± 5.2 months. 37 of the 67 (55.2%)
patients had positive immunohistochemical staining of p-ERK1/2, and 35 (52.2%) had positive PI3K staining. The relevance of positive p- ERK1/2 and PI3K expression to patients survival was examined by univariate Kaplan-Meier survival analysis. Overall survival was inversely associated with positive or increased expression Alvespimycin cost of p-ERK1/2 (P = 0.045) (Figure 3a) and PI3K (P = 0.062) (Figure 3b). The relevance of overall survival and other clinical pathological characteristics were also assessed by univariate analysis which showed that the overall 4SC-202 survival was associated with tumor pathological type (P = 0.031), tumor diameter (P = 0.003), lymph node metastasis (P = 0.005) and surrounding tissue invasion (P = 0.002). All factors that showed significant association in the univariate Kaplan-Meier analysis were subsequently subject to multivariate Cox regression survival analysis, which indicated that lymph node metastasis and surrounding tissue invasion were the most significant predictors of short overall survival, followed
by p-ERK1/2 over-expression (Table 4). Figure 3 Kaplan-Meier plots for overall survival in 67 patients with gallbladder carcinoma surgery in relation to p-ERK1/2 and PI3K expression. (a) Positive or increased p-ERK1/2 expression
was associated with reduced over survival (P = 0.045, log rank test). (b) Increased PI3K expression was also related to reduced overall survival (P = 0.062, log rank test). Table 4 Multivariate Cox regression analysis of overall survival in 67 patients with surgical resection of gallbladder carcinoma. Group Category SE(B) P 95% CI for Exp(B) Inferior Superior Pathology type Adenoma canceration/well-/moderately-/poorly-differentiated/mucous adenoma 1.73 0.249 0.82 2.15 Tumor diameter <2.0 cm/≥2.0 cm 2.08 0.041 1.01 3.99 Lympho node metastasis No/Yes 2.58 0.019 1.21 3.97 Surrounding tissue invasion No/Yes 2.46 0.025 Inositol monophosphatase 1 1.17 3.86 p-ERK1/2 -/+ 2.35 0.028 1.07 4.19 PI3K -/+ 2.24 0.037 1.03 4.03 SE = Standard Error, B = Beta, CI = Confidence Interval. Discussion In the present study, we examined p-ERK1/2 and PI3-K expression by immunohistochemistry in 108 human gallbladder adenocarcinoma samples from separate individuals. 58.3% and 50.9% of the specimens showed strong positive staining for p-ERK1/2 and PI3-K, respectively, indicating that both p-ERK1/2 and PI3-K/AKT might be potential biomarkers of gallbladder cancer. Compared to benign lesions and peri-tumor tissues, positive staining for p-ERK1/2 and PI3-K in gallbladder adenocarcinoma was significantly higher. Expression of p-ERK1/2 and PI3-K was correlated with a low grade of differentiation in adenocarcinoma (Table 1).