The effects of two combined methods of P53 expression and preoperative serum CEA detection on the prognosis of colorectal cancer

Abstract

Aim: To explore the effects of two combined methods-P53 expression and preoperative serum carcinoembryonic antigen (S-CEA) detection-on the prognosis of colorectal cancer (CRC).

Methods: Two classified combinations of tissue P53 and S-CEA were utilized: Combined P53 groups (normal P53 and S-CEA, or one or both elevated) and Recombined groups (P53 normal & S-CEA normal, P53 normal & S-CEA high, P53 high & S-CEA normal, P53 high & S-CEA high). Clinicopathologic features were analyzed by P53, S-CEA, Combined P53, and Recombined P53. Correlations between them were examined. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Log-Rank test. Univariate and multivariate analyses were performed for Combined P53 and Recombined P53 to determine independent factors. Three-year, two-year, and one-year OS and DFS were further analyzed using multimeROC. SPSS 27 and R 4.4.1 were used for analysis.

Results: TNM stage, CA199, differentiation, tumor maximum size, and minimum size showed significant differences between the single P53 and S-CEA groups (all P < 0.05). TNM stage, CA199, and chemotherapy differed in both Combined P53 and Recombined P53 groups (all P < 0.05). Significant correlations were found between P53, S-CEA, Combined P53, and Recombined P53 (all P < 0.001). No significant differences in OS and DFS were observed with P53 and Combined P53 (all P > 0.05), but differences were noted with S-CEA and Recombined P53 (all P < 0.05). Univariate and multivariate analyses identified laparoscopy, chemotherapy, differentiation, TNM stage, and Recombined P53 as independent factors for OS and DFS, while P53, S-CEA, and Combined P53 were not. Further multimeROC analysis showed that 3-year OS had better sensitivity and specificity (Area Under Curve [AUC] = 0.54), and 1-year DFS was better (AUC = 0.59).

Conclusions: Recombined P53 classification was more effective than traditional Combined P53 classification for assessing CRC prognosis and was an independent factor. Additionally, the 3-year OS and 1-year DFS analysis demonstrated higher sensitivity and specificity with Recombined P53.

Keywords: CEA; CRC; DFS; OS; ROC; p53; prognosis.

Figure 1

Pictures of p53 tumor expression. (A) Normal p53 expression (left: × 200, right: ×400); (B) High p53 expression (left: ×200, right: ×400). No positive cells or positive cells <5% are negative, positive cells 5%– 25% are weakly positive (+), 25% ~75% is positive (++), >75% is strong positive (+++). We refer to patients with p53 staining greater than 75% as the p53 high- expression group, and the rest as the normal group (6).

Figure 2

Overall survival (OS) and Disease free survival (DFS) analysis with number at risk by Kaplan-Meier and Log-rank test using R 4.4.1. (A) By p53 groups, there are no significant differences about OS (P=0.65) and DFS (P=0.9); (B) By S-CEA groups, there are significant differences about OS (P<0.001) and DFS (P<0.001); (C) By combined p53 groups, there are no significant differences about OS (P=0.16) and DFS (P=0.087); (D) By recombined p53, there are significant differences about OS (P=0.0073) and DFS (P=0.0022).

Figure 3

Receiver operating characteristic curve analysis (ROC) by multitimeROC using R4.4.1. (A) ROC analysis using OS (Binary variable), Area Under Curve (AUC) were 0.47,0.47 and 0.54 respectively for 1,2,3 years indicating 3 years has superior. (B) ROC analysis using DFS (Binary variable), Area Under Curve (AUC) were 0.59, 0.57 and 0.51 respectively for 1,2,3 years indicating 1 year has superior.