肝转移是恶性肿瘤治疗中的主要挑战。基因组分析在恶性肿瘤的诊断、治疗和预后预测中的应用越来越广泛。在本研究中，我们构建了一个基于基因突变的风险模型来预测肝转移的生存情况。我们在纪念斯隆-凯特琳癌症中心（MSKCC）数据集中选择了800名肝转移患者构建了风险模型，并从其他四个队列中收集了另外794名肝转移患者进行验证。此外，对51名既有体细胞突变数据又有RNA测序数据的乳腺癌肝转移（BCLM）患者进行了肿瘤微环境（TME）和体细胞突变的分析。我们构建了一个涉及10个基因的基因突变风险模型来将肝转移患者分为高风险组和低风险组。低风险组的患者比高风险组的患者有更长的生存时间，这一结果在训练和验证队列中均有观察到。BCLM的TME分析显示，低风险组表现出更多的免疫浸润。此外，在BCLM患者中，高风险组的突变特征与低风险组完全不同。我们的研究构建的基因突变风险模型展示了预测肝转移预后的可靠能力。BCLM患者不同风险评分的TME和体细胞突变差异可以指导进一步的研究和治疗决策。© 2023. BioMed Central Ltd., part of Springer Nature.

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.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.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.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.© 2023. BioMed Central Ltd., part of Springer Nature.