Correlation Of The Expression Of TBX-2 With P14^ARF And E2F And Their Effects On Prognosis Of Colorectal Carcinoma

Objective: To investigate the correlation of the expression of TBX-2 with P14^ARF, E2F1 and E2F3 in colorectal carcinoma tissues, and the relationship between the expression of TBX-2, P14^ARF, E2F1, E2F3 and the clinicopathological characteristics, prognosis. It also have the potential of providing theoretical basis for the prevention, early diagnosis and prognosis prediction of tumor, and have the potential of providing target for the treatment of gene.Methods: Immunohistochemical SP staining was used to detect the expressions of TBX-2, P14^ARF, E2F1 and E2F3 proteins in 60 colorectal carcinoma tissues and 20 adjacent normal tissues. The correlations of TBX-2, P14^ARF, E2F1 and E2F3 with clinicopathological factors were analyzed by x2 test or Fisher's exact test; Overall survival rate was computed by the life table. method and Kaplan-Meier estimate. The log-rank test was used to compare survival curves by obtaining a x2 value. A multivariate proportional hazard medel (Cox model) was used to test the prognostic effect of all factors on study. All data were analyzed using SAS software version 8.2.Result:1. The positive rates of TBX-2, P14^ARF, E2F1 and E2F3 in the adjacent normal tissues and colorectal carcinoma tissues were 70.0%, 71.7%, 68.3%, 20.0% and 70.0%, 71.7%, 68.3%, 20.0% respectively. Expression of TBX-2 and E2F1 in colorectal carcinoma were higher than that in normal mucosa (P<0.05), and that of P14^ARF and E2F3 in colorectal carcinoma were lower than that in normal mucosa (P<0.05).2. The expression of TBX-2, P14^ARF, E2F1 in colorectal carcinoma tissues were correlated with the tumor stage, lymph node metastasis (P<0.05), P14^ARF and E2F1 were also correlated with the differentiation degree(P<0.05). And they were not corre1ated with age, sex, the position of tumor occurrence, diameter of tumor and other clinicopathological factors. The expression of E2F3 in cancer tissues was not correlated with the clinicopathological characteristics. 3. The expression of TBX-2 had negative correlation with expression of P14^ARF (r=-0.348, P<0.05), but had positive correlation with the expression of E2F1 (r=0.336, P<0.05). P14^ARF had negative correlation with expression of E2F1 (r=-0.279,P<0.05).4. In univariate analysis, the expression of TBX-2, P14^ARF, E2F1, 1ymph node metastasis, Dukes stage were associated with poor survival in colorectal carcinoma; there were no association between age, sex, the tumor stage, differentiation degree, the expression of E2F3 and the overall survival of colorectal carcinoma patients.5. In multivariate analysis, the expression of P14^ARF and 1ymph node metastasis,Dukes stage were independent prognostic factors of colorectal carcinoma(P<0.05).Conclusions:1. Expression of TBX-2 and E2F1 were highly up-regulated and P14^ARF was down-regulated in colorectal carcinoma tissues. They were associated with 1ymph nodes metastasis, the tumor stage and the differentiation degree. They may have the important significance on forecasting the invasion and metastasis of colon carcinomas. E2F3 was lowly expressed in colorectal carcinomas, and the expression of E2F3 in cancer tissues was not correlated with the tumor stage,pathological type,lymph node metastasis and the depth of invasion, and the anomalous expression of E2F3 gene may permit the colorectal tumorigenesis and progression.2. The expression of TBX-2, P14^ARF, E2F1 in colorectal carcinoma tissues were correlated with each other.3. The lower expression of P14^ARF and 1ymph node metastasis, Dukes stage reflected poor prognosis of patient with colorectal carcinoma, P14^ARF protein may be a sensitive biomarker for the prognosis predict of colorectal carcinoma.