A gene mutation-based risk model for prognostic prediction in liver metastases

Abstract

Background Liver metastasis is the major challenge in the treatment for malignant tumors. Genomic profiling is increasingly used in the diagnosis, treatment and prediction of prognosis in malignancies. In this study, we constructed a gene mutation-based risk model to predict the survival of liver metastases. Method We identified the gene mutations associated with survival and constructed the risk model in the training cohort including 800 patients with liver metastases from Memorial Sloan-Kettering Cancer Center (MSKCC) dataset. Other 794 patients with liver metastases were collected from 4 cohorts for validation. Furthermore, the analyses of tumor microenvironment (TME) and somatic mutations were performed on 51 patients with breast cancer liver metastases (BCLM) who had both somatic mutation data and RNA-sequencing data. Results A gene mutation-based risk model involved 10 genes was constructed to divide patients with liver metastases into the high- and low-risk groups. Patients in the low-risk group had a longer survival time compared to those in the high-risk group, which was observed in both training and validation cohorts. The analyses of TME in BCLM showed that the low-risk group exhibited more immune infiltration than the high-risk group. Furthermore, the mutation signatures of the high-risk group were completely different from those of the low-risk group in patients with BCLM. Conclusions The gene mutation-based risk model constructed in our study exhibited the reliable ability of predicting the prognosis in liver metastases. The difference of TME and somatic mutations among BCLM patients with different risk score can guide the further research and treatment decisions for liver metastases.