Hierarchical investigating the predictive value of p53, COX2, EGFR, nm23 in the post-operative patients with colorectal carcinoma

Abstract

The aim of this study was to evaluate the correlations between p53, COX2, EGFR, nm23 expression and the progression free survival (PFS) of post-operative patients with colorectal carcinoma. Immunohistochemistry was used to detect the expression of p53, COX2, EGFR and nm23 in 459 specimens from colorectal carcinoma patients. Kaplan-Meier estimates, Cox proportional hazard regression analyses and hierarchical analyses were performed on the collected data. Kaplan-Meier estimates analysis suggested that EGFR expression was as a negative predictor, the median PFS of patients with EGFR high expression was 21.73 months, and the median PFS of patients with low EGFR expression was 57.83 months (χ2=20.880, P<0.001); nm23 expression was positive predictive factor for the prognosis of patients with colorectal carcinoma, the median PFS of patients with high nm23 expression was 37.77 months, and the median PFS was 21.47 months in the patients with low nm23 expression (χ2=7.364, P=0.007). Cox regression analysis revealed that comparing with the patients with low expression of EGFR, the patients with high EGFR expression were at higher risk of tumor progression (HR=1.667, P=0.004); Comparing with the patients with high nm23 expression, the patients with nm23 low expression had a higher risk of tumor progression (HR=0.412, P<0.001); and the risk of tumor progression was higher in the patients with high EGFR expression and low nm23 expression (HR=0.245, P<0.001). Hierarchical analysis showed that EGFR expression mainly correlates with the PFS of TNM stage I-II colorectal cancer patients, the median PFS was 33.53 months in the TNM stage I-II colorectal cancer patients with high EGFR expression patients; The median PFS of the TNM stage I-II colorectal cancer patients with low EGFR expression was 70.43 months (χ2=9.530, P=0.002); The median PFS was 19.2 months in the TNM stage III-IV colorectal cancer patients with high expression EGFR, the PFS of the TNM stage III-IV colorectal cancer patients with low EGFR expression was 37.87 months (χ2=7.97, P=0.005). nm23 expression mainly correlates with the PFS of TNM stage III-IV colorecatal cancer patients. The median PFS was 47.27 months in TNM stage I-II colorectal cancer patients with nm23 high expression, the median PFS was 48.85 months in TNM stage I-II colorectal cancer patients with low nm23 expression (χ2=0.101, P=0.750); The median PFS was 28.8 months in TNM stage III-IV colorectal cancer patients with nm23 high expression, the median PFS was 14.7 months in TNM stage III-IV colorectal cancer patients with low nm23 expression (χ2=13.213, P<0.001). EGFR is mainly a predictive factor for the prognosis of post-operative patients with TNM stage I-II colorectal cancer, and nm23 is important for predicting the prognosis of patients with stage III-IV, and EGFR and nm23 could be as predictor of combination.

Keywords: EGFR; colorectal carcinoma; nm23; post-operative.

Figure 1. Immunohistochemistry results

The expression of EGFR A. and B., nm23 C. and D., p53 E. and F., and COX2 G. and H. in patients derived sections.

Figure 2. Statistical analyses for the correlation between PFS and the protein expression of p53, COX2, EGFR, nm23, and EGFR&nm23 combined

The expression of p53 A. and COX2 COX2 B. were not related to PFS. The expression of EGFR C. and nm23 D. were highly associated with PFS. And the PFS of patients with low EGFR and high nm23 expression E. was significantly different than those with high EGFR and low nm23 expression.

Figure 3. Hierarchical analysis of the correlation between PFS and the expression of p53, COX2, EGFR, nm23 in the patients with TNM stage I-II and III-IV

p53 A. and B. and COX2 C. and D. had not statistical significance to the PFS of post-operative patients with colorectal carcinoma, instead of EGFR E. and F. and nm23 G. and H., and the results suggested that high EGFR expression promoted the cancer progression of the post-operative patients with colorectal cancer in TNM stage I-II, and the nm23 expression mainly influenced the PFS of the patients with TNM stage III-IV.

Figure 4. Hierarchical analysis of the relationships between PFS and the expression of EGFR, COX2, p53, nm23 in the patients with pathological grade I-II and III-IV

p53 A. and B. and COX2 C. and D. had not statistical significance to the PFS of post-operative patients with colorectal carcinoma, instead of EGFR E. and F. and nm23 G. and H., and the results suggested that high EGFR expression promoted the cancer progression of the post-operative patients with colorectal cancer in pathological grade I-II, and the nm23 expression mainly influenced the PFS of the patients with pathological grade III-IV.