作为全球最常见的胃肠道恶性肿瘤，肝转移瘤发生在半数结直肠癌（CRC）患者身上。早期检测可以帮助早期治疗，并降低结直肠癌肝转移瘤（CRLM）患者的死亡率。因此，寻找有用的CRLM生物标志物至关重要。我们使用TCGA和GEO数据库下载了患者的表达谱和临床数据。差异分析筛选了与CRLM相关的基因，并通过单变量Cox回归分析确定了与预后相关的基因。最小绝对收敛和选择算子（LASSO）方法进一步选择基因来构建预后标记。使用Kaplan-Meier生存曲线显示患者的总体生存（OS）。接收工作特征（ROC）曲线显示模型的准确性。将患者的风险评分和临床特征包括在多变量Cox回归分析中，以确定独立危险因素，并构建一种诊断曲线图。使用'CIBERSORT'和'ESTIMATE'软件包评估免疫细胞比例和浸润情况。我们构建了一个由七个与CRLM相关的基因组成的预后标记，并且基于该标记的风险评分在估计CRC患者的预后方面具有巨大潜力。此外，高风险患者对免疫治疗的不良反应可能促使个体的不良预后。此外，我们发现在CRC和肝转移组织中，唯一高表达的基因Hepcidin抗菌肽（HAMP）的过表达促进了CRC的发展，并与各种肿瘤中的肿瘤突变负担（TMB），DNA错配修复（MMR）基因和微卫星不稳定性（MSI）相关。最后，我们发现在CRC患者中，HAMP的低表达也代表了更好的免疫治疗结局，反映了HAMP在指导免疫治疗中的重要作用。我们确定了一个包含7个与CRLM相关的基因的预后标记，该标记作为独立预测因子，并相应建立了一个包含风险评分的诊断曲线图。此外，衍生基因HAMP可以帮助指导有益的免疫治疗策略的探索。2023年版权所有，刘氏、鲁氏、严氏、薛氏、何氏、黄氏、孙氏、赵氏、李氏。

As the most common gastrointestinal malignancy worldwide, liver metastases occur in half colorectal cancer (CRC) patients. Early detection can help treat them early and reduce mortality in patients with colorectal cancer liver metastases (CRLM). Finding useful biomarkers for CRLM is thus essential.The TCGA and GEO databases were used to download the expression profiles and clinical data of the patients. Differential analysis screened for genes associated with CRLM, and univariate Cox regression analysis identified genes associated with prognosis. The least absolute shrinkage and selection operator (LASSO) method further preferred genes to construct a prognostic signature. Kaplan-Meier survival curves were used to show patients' overall survival (OS). Receiver operating characteristic (ROC) curves showed the accuracy of the model. Risk scores and clinical characteristics of patients were included in multivariate Cox regression analysis to identify independent risk factors, and a nomogram was constructed. The proportion of immune cells and infiltration were assessed using the 'CIBERSORT' package and the 'ESTIMATE' package.We constructed a signature consisting of seven CRLM-associated genes, and signature-based risk scores have great potential in estimating the prognosis of CRC patients. Moreover, the poor response to immunotherapy in high-risk patients might contribute to the poor prognosis of individuals. Furthermore, we found that overexpression of Hepcidin antimicrobial peptide (HAMP), the only gene highly expressed in CRC and liver metastatic tissues, promoted CRC development and that it was associated with tumor mutation burden (TMB), DNA mismatch repair (MMR) genes, and microsatellite instability (MSI) in various tumors. Finally, we found that in CRC patients, low expression of HAMP also represented a better immunotherapeutic outcome, reflecting the critical role of HAMP in guiding immunotherapy.We identified a prognostic signature containing 7 CRLM-associated genes, and the signature was specified as an independent predictor and a nomogram containing the risk score was built accordingly. In addition, the derived gene HAMP could help guide the exploration of profitable immunotherapeutic strategies.Copyright © 2023 Liu, Lu, Yan, Xue, He, Huang, Sun, Zhao and Li.