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Abstract：
Colorectal cancer (CRC) remains a significant contributor to cancer-related mortality, emphasizing the critical need for identifying biomarkers that can improve clinical management and patient outcomes. In this retrospective study, we analyzed tumor samples from 25 patients with metastatic CRC, categorized based on long-term (> 50 months) or short-term (< 10 months) survival. Employing the PanCancer Immune Profile Panel, encompassing 770 genes, in the discovery dataset, we identified 54 differentially expressed genes (DEGs) within the tumor microenvironment of metastatic CRC. Validation of potential biomarkers was performed using two publicly available RNA-based sequencing datasets (TCGA 1 (n=371) and TCGA 2 (n=566)). Univariate COX regression unveiled that three significant biomarkers were associated with overall survival in CRC within the discovery dataset, which were SLC11A1 (hazard ratio (HR): 4.09, P=0.012), TNFSF11 (HR: 3.67, P=0.02), and MEF2C (HR: 0.34, P=0.037). Kaplan-Meier survival curve analyses confirmed the correlation between SLC11A1 expression and overall survival in CRC across the discovery set (P=0.0071) and the two independent datasets (TCGA 1 (P=0.0016) and TCGA 2 (P=0.025)). Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.64 to 0.76, with sensitivity of 59% to 87% and specificity of 60% to 73% for predicting CRC overall survival. Immunohistochemistry staining further validated the strong expression of SLC11A1 protein in CRC tumor cells, with high expression correlating with short-term survival. These findings suggest that SLC11A1 serves as a predictive biomarker for overall survival in CRC patients.
摘要：
结直肠癌（CRC）仍然是癌症相关死亡率的重要因素。强调迫切需要确定可以改善临床管理和患者预后的生物标志物。在这项回顾性研究中,我们分析了25例转移性CRC患者的肿瘤样本，根据长期（>50个月）或短期（<10个月）生存期进行分类。利用PanCancer免疫概况小组，包括770个基因，在发现数据集中，我们在转移性CRC的肿瘤微环境中鉴定出54个差异表达基因(DEGs).使用两个公开可用的基于RNA的测序数据集(TCGA1(n=371)和TCGA2(n=566))进行潜在生物标志物的验证。单变量COX回归揭示了发现数据集中三种显著的生物标志物与CRC的总生存期相关。SLC11A1（危险比（HR）：4.09，P=0.012），TNFSF11（HR：3.67，P=0.02），和MEF2C（HR：0.34，P=0.037）。Kaplan-Meier存活曲线分析证实了发现集（P=0.0071）和两个独立数据集（TCGA1（P=0.0016）和TCGA2（P=0.025））中SLC11A1表达与CRC总生存期之间的相关性。受试者工作特征曲线分析显示，曲线下面积为0.64至0.76，预测CRC总体生存率的敏感性为59％至87％，特异性为60％至73％。免疫组化染色进一步验证了SLC11A1蛋白在CRC肿瘤细胞中的强表达,与短期生存相关的高表达。这些发现表明SLC11A1作为CRC患者总体生存的预测生物标志物。
