Prognostic value of a novel biomarker combining DNA ploidy and tumor burden score for initially resectable liver metastases from patients with colorectal cancer

Background Colorectal cancer liver metastases (CRLM) has not been identified as a unified disease entity due to the differences in the severity of metastatic disease and tumor aggressiveness. A screen for specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM. Methods One hundred thirty-nine consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. DNA ploidy, stroma fraction and nucleotyping of liver metastases were evaluated using automated digital imaging systems. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression models. Results DNA ploidy was identified as an independent prognostic factor for RFS (HR, 2.082; 95% CI 1.053-4.115; P = 0.035) in the multivariate analysis, while stroma-tumor fraction and nucleotyping were not significant prognostic factors. A significant difference in 3-year RFS was observed among the low-, moderate- and high-risk groups stratified by a novel parameter combined with the tumor burden score (TBS) and DNA ploidy (72.5% vs. 63.2% vs. 37.3%, P = 0.007). The high-risk group who received adjuvant chemotherapy had a significantly better 3-year RFS rate than those without adjuvant chemotherapy (46.7% vs. 24.8%; P = 0.034). Conclusions Our study showed that DNA ploidy of liver metastases is an independent prognostic factor for patients with initially resectable CRLM after liver resection. The combination of DNA ploidy and TBS may help to stratify patients into different recurrence risk groups and may guide postoperative treatment among the patients. Keywords: Colorectal cancer, Liver metastases, DNA ploidy, Stroma fraction, Nucleotyping, Prognosis