| Objective:Gastric cancer (GC) is usually diagnosed at an advanced stage when therapies are very limited. Identification of high risk factors and appropriate management of these risk factors could reduce the incidence of GC and may be helpful for early detection and good prognosis. Intestinal metaplasia (IM) have been recognized as premalignant lesions of GC. TAZ, P53 and P16 have been shown to differentiate between benign and malignant lesions but the relationship between them ingastric samples was rarely reported. The present study aimed to investigate expression of TAZ, P53 and P16 in different gastric lesions especially in simple atypical intestinal metaplasia (SIM), atypical intestinal metaplasia (AIM) and carcinoma, estimate the correlation between them and explore their possible roles in the tumor genesis and development of gastric cancer as well as their clinic pathological significance.Methods:The expression of TAZ、P53 and P16 were detected by immunohistochemistry of 194 GC samples, and analyzed with complete clinicopathological features. Overall survival rates were also calculated using the Kaplan-Meier method. Cox proportional hazard model was performed to assess the prognostic values.74 normal mucosa,32 SIM,51 AIM and 37 dysplasia samples were studied comparably.Results: TAZ and P53 protein expression was significantly higher in AIM, dysplasia and GC than that in normal mucosa and SIM whilethe expression of P16 in AIM and dysplasia were significantly higher than the other groups (P< 0.05). Remarkable positive correlations were found between expression of TAZ and P53 in AIM (r=0.317, P= 0.024), dysplasia (r= 0.339,P= 0.039) and GC (r=0.183,P=0.011);negative correlation was only found between TAZ and P16 in normal mucosa (r= 0.018, P=-0.274); no correlation was found in P53 and P16 in all groups.Overexpression of TAZ in GC was markedly correlated with T status which represents depth of invasion (P=0.005) and TNM stage (P= 0.001). The abnormal expression of P53 in GC was significantlycorrelated with T status (P=0.045) and tumor size (P=0.037). The abnormal expression of P16 in GC was markedly correlated with age(P=0.013),differentiation (P=0.039) and TNM stage (P=0.024). When the GC cases were analyzed by Kaplan-Meier curves, we observed that the abnormal expression of TAZ, P53, P16 and TAZ& P53 significantly affected overall survival rate of GC patients (P<0.05 for all).The Cox univariate model highlighted that abnormal expression of TAZ, P53, TAZ& P53 and P16, anatomical site, tumor size, T status (Depth of invasion), N status (Lymph node status) and TNM stage significantly impact overall survival time (P< 0.05 for all). Multivariate analysis revealed that TAZ expression (HR2.502, CI 95%, 1.343-4.661, P=0.004), P16 expression (HR 1.831, CI 95%,1.159-2.894, P=0.010) and tumor size (HR 1.592,CI95%,1.025-2.472, P=0.038) were independent prognostic variables influencing OS.Conclusions:Compared with SIM, AIM has more potential to progress to GC. It may be an effective criterion by which to diagnose early GC in the clinical follow-up of AIM patients. IM patients could be detected by TAZ and P16 to assess the risk for cancer. Our research demonstrated that expression of TAZ were positively associated with P53 in AIM, dysplasia and GC indicating that TAZ may interact with P53 in the later process of GC promotion. Moreover, abnormal expression of TAZ and P16 could be independent predictors of prognosis in GC, so targeting TAZ and P16 could prove to be promising therapeutic strategies for the treatment of GC. |
PDF Full Text Request