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Abstract：
Colorectal liver metastasis (CRLM) is challenging in the clinical treatment of colorectal cancer. Limited research has been conducted on how CRLM develops. RNA sequencing data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Four machine learning algorithms were used to screen the hub CRLM-specific genes, including Least Absolute Shrinkage and Selection Operator (Lasso), Random forest, SVM-RFE, and XGboost. The model for identifying CRLM was developed using stepwise logistic regression and was validated using internal and independent datasets. The prognostic value of hub CRLM-specific genes was assessed using the Lasso-Cox method. The in vitro experiments were performed using SW620 cells. The CRLM identification model was developed based on four CRLM-specific genes (SPP1, ZG16, P2RY14, and PRKAR2B), and the model efficacy was validated using GSE41258 and three external cohorts. Five CRLM-specific prognostic hub genes, SPP1, ZG16, P2RY14, CYP2E1, and C5, were identified using the Lasso-Cox algorithm, and a risk score was constructed. The risk score was validated using the GSE39582 cohort. Three genes have both efficacy in identifying CRLM and prognostic value: ZG16, P2RY14, and SPP1. Immune infiltration and enrichment analyses demonstrated that SPP1 was associated with M2 macrophage polarization and extracellular matrix remodeling. In vitro experiments indicated that SPP1 may act as a cancer-promoting factor. The hub CRLM-specific gene SPP1 can help determine the diagnosis, prognosis, and immune infiltration of patients with CRLM.
摘要：
结直肠癌肝转移(CRLM)在结直肠癌的临床治疗中具有挑战性。对CRLM的发展进行了有限的研究。从基因表达综合(GEO)和癌症基因组图谱(TCGA)获得RNA测序数据。四种机器学习算法用于筛选集线器CRLM特定基因，包括最小绝对收缩和选择算子(Lasso)，随机森林,SVM-RFE,和XGboost。使用逐步逻辑回归开发了用于识别CRLM的模型，并使用内部和独立的数据集进行了验证。使用Lasso-Cox方法评估中枢CRLM特异性基因的预后价值。使用SW620细胞进行体外实验。基于四个CRLM特异性基因（SPP1，ZG16，P2RY14和PRKAR2B）开发了CRLM鉴定模型，模型疗效使用GSE41258和三个外部队列进行验证.五个CRLM特异性预后中枢基因，SPP1、ZG16、P2RY14、CYP2E1和C5使用Lasso-Cox算法进行鉴定，并构建了风险评分。使用GSE39582队列验证风险评分。三个基因在鉴定CRLM和预后价值方面都有功效：ZG16，P2RY14和SPP1。免疫浸润和富集分析表明，SPP1与M2巨噬细胞极化和细胞外基质重塑有关。体外实验表明，SPP1可能是一种促癌因子。集线器CRLM特异性基因SPP1可以帮助确定诊断，预后,和CRLM患者的免疫浸润。
