Differential genetic variations and prognostic predicting factors in colorectal cancer patients with or without liver metastasis.

Abstract

e16049 Background: Although liver metastasis is the most common metastasis for colorectal cancer (CRC), the molecular mechanism determining the metastasis has not been clarified. Our study aims to investigate the potential molecular mechanisms of liver metastasis by comparing the genetic variations between patients with or without liver metastasis, and to explore the prognostic factors for the two groups of patients. Methods: 57 stage I-IV CRC patients (49 with stage III/IV) were enrolled. 26 patients had no liver metastasis while 31 patients had liver metastasis when they were recruited. Whole-exome sequencing was performed on the primary cancer tissues of all patients. All patients were followed up for up to 50 months. Results: We found that the tumor mutation burden (TMB) of primary cancer tissue from patients with liver metastasis was significantly higher than those without metastasis (P < 0.05). When the mutation frequency was compared at whole-exome level, the mutation frequency of TCF7L2 and TRIM77 genes of primary cancer tissues was found to be significantly higher in patients with liver metastasis (TCF7L2: 35.48% vs. 3.85% (P = 0.0037) for patients with or without metastasis; TRIM77: 16.13% vs. 0% (P = 0.050) for patients with or without metastasis). Further study revealed that in patients with liver metastasis, patients with TRIM77 mutations showed worse overall survival (OS) than those without TRIM77 mutations (P < 0.0001). Similarly, patients with 7_12p.13.33 amplification, 10_14q32.33 amplification, and 4_10q23.31 deletion showed worse OS than those without the mutations (P < 0.05). In contrast, in patients without liver metastasis, patients with 6_20q13.33 amplification showed worse OS than those without the amplification. Conclusions: The TMB of CRC patients with liver metastasis was significantly higher than those without liver metastasis. TCF7L2 and TRIM77 gene mutations may be predictive for liver metastasis. TRIM77 mutation, 7_12 p.13.33 amplification, 10_14q32.33 amplification, and 4_10q23.31 deletion were related to poor OS in patients with liver metastasis, while 6_20q13.33 amplification was related to poor OS in patients without liver metastasis.