Liu Chang, Lu Zhihua, Yan Jun, Xue Dong, He Xiaoyu, Huang Wenbo, Sun Qi, Zhao Wei, Li Fanni
Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.
Front Oncol. 2023 Jul 26;13:1234045. doi: 10.3389/fonc.2023.1234045. eCollection 2023.
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.
作为全球最常见的胃肠道恶性肿瘤，半数结直肠癌（CRC）患者会发生肝转移。早期检测有助于早期治疗并降低结直肠癌肝转移（CRLM）患者的死亡率。因此，寻找CRLM的有用生物标志物至关重要。
利用TCGA和GEO数据库下载患者的表达谱和临床数据。差异分析筛选与CRLM相关的基因，单变量Cox回归分析确定与预后相关的基因。最小绝对收缩和选择算子（LASSO）方法进一步优选基因以构建预后特征。Kaplan-Meier生存曲线用于显示患者的总生存期（OS）。受试者工作特征（ROC）曲线显示模型的准确性。将患者的风险评分和临床特征纳入多变量Cox回归分析以确定独立危险因素，并构建列线图。使用“CIBERSORT”软件包和“ESTIMATE”软件包评估免疫细胞的比例和浸润情况。
我们构建了一个由7个与CRLM相关的基因组成的特征，基于特征的风险评分在估计CRC患者的预后方面具有很大潜力。此外，高危患者对免疫治疗反应不佳可能导致个体预后不良。此外，我们发现铁调素抗菌肽（HAMP）是CRC和肝转移组织中唯一高表达的基因，其过表达促进了CRC的发展，并且它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低表达也代表了更好的免疫治疗结果，这反映了HAMP在指导免疫治疗中的关键作用。
我们鉴定了一个包含7个与CRLM相关基因的预后特征，并将该特征指定为独立预测因子，据此构建了包含风险评分的列线图。此外，衍生基因HAMP有助于指导探索有效的免疫治疗策略。
