431) or the 5-FU-treated group (overall log rank P=0.112) (data not shown). For each patient, the ratio of Bax/Bcl2 expression was determined and correlated with patient
survival separately for each treatment category. The ratio of Bax/Bcl2 expression was not correlated with patient survival in surgery alone category (Fig 3C). In contrast, the ratio of Bax/Bcl2 expression significantly correlated with patient survival, indicating that those patients with a high Bax/Bcl2 ratio value would not benefit from 5-FU treatment; however, those patients with low Bax/Bcl2 ratios were more OSI-906 in vivo likely to have better survival when treated with Inhibitors,research,lifescience,medical 5-FU based therapies (Fig 3D). Analysis of nuclear accumulation Inhibitors,research,lifescience,medical of p53 Expression of p53nac was generally homogenous; however, p53 staining was observed in the cytoplasm of malignant cells in 7% of cases (8 of 112) (Fig 2G-I). The cytoplasmic staining was not further analyzed. High levels of p53nac were found in tumors of 59% of patients (33 5-FU-treated and 32 surgery-alone). For both categories of patients, there were no significant differences in the incidence of deaths due to CRCs (Table 1), in the median survival (Table 3), or survival rates (data not shown) in relation to p53nac (Table 1). Multivariate survival analyses As determined by multivariate analyses of Cox proportional hazards, surgery-alone patients with low Bax expression had 5.33 Inhibitors,research,lifescience,medical times Inhibitors,research,lifescience,medical higher mortality compared to those with
high Bax expression (HR: 5.33; CI: 1.78-15.94) when adjusted for demographic and clinicopathological variables and for expression Bcl-2, the Bax/Bcl2 ratio, and p53nac (Table 4). 5-FU treated patients with low Bax/Bcl2 ratios had 21.55 times higher mortality compared to those with high Bax/Bcl2 ratios (HR: 21.55; CI: 1.46-31.00), when adjusted for other variables (Table 4). Bcl-2 and p53nac, however, were not independent prognostic indicators of survival in either group of patients (Table 4). Table 4 Multivariate Cox regression analyses Inhibitors,research,lifescience,medical to assess the prognostic
significance of clinicopathological and molecular features based on treatment status on overall survival Discussion The current study, we analyzed the predictive value of Bax, Bcl-2, and p53nac and determined their isothipendyl association with survival in CRC patients who received 5-FU-based adjuvant treatment after surgery and in CRC patients matched for age, gender, ethnicity, tumor stage, tumor location, and tumor differentiation who underwent surgery alone with curative or palliative intent. These analyses demonstrate a better survival of patients who received chemotherapy when their CRCs lacked Bax expression. In contrast, patients with CRCs that exhibited high Bax expression had worse survival when they received 5-FU-based adjuvant chemotherapy. Furthermore, multivariate Cox regression analysis showed that surgically treated patients with low levels (or lack) of Bax expression had 5.