Hsu Hung-Chih, Lee Yun-Shien, Imbang Titilianty I, Liu Ting-Chia, Hung Shuen-Iu
Division of Hematology-Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 333, Taiwan.
College of Medicine, Chang Gung University Linkou, Taoyuan 333, Taiwan.
Am J Cancer Res. 2024 Jun 15;14(6):2839-2851. doi: 10.62347/VTYU3157. eCollection 2024.
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.
结直肠癌(CRC)仍然是癌症相关死亡的一个重要因素,这凸显了识别能够改善临床管理和患者预后的生物标志物的迫切需求。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,并根据长期(>50个月)或短期(<10个月)生存情况进行分类。在发现数据集中,我们使用包含770个基因的泛癌免疫谱面板,在转移性CRC的肿瘤微环境中鉴定出54个差异表达基因(DEG)。使用两个公开可用的基于RNA的测序数据集(TCGA 1(n = 371)和TCGA 2(n = 566))对潜在生物标志物进行验证。单变量COX回归显示,在发现数据集中,有三个重要的生物标志物与CRC的总生存相关,分别是SLC11A1(风险比(HR):4.09,P = 0.012)、TNFSF11(HR:3.67,P = 0.02)和MEF2C(HR:0.34,P = 0.037)。Kaplan-Meier生存曲线分析证实了在整个发现集(P = 0.0071)以及两个独立数据集(TCGA 1(P = 0.0016)和TCGA 2(P = 0.025))中,SLC11A1表达与CRC总生存之间的相关性。受试者工作特征曲线分析表明,曲线下面积在0.64至0.76之间,预测CRC总生存的敏感性为59%至87%,特异性为60%至73%。免疫组织化学染色进一步验证了SLC11A1蛋白在CRC肿瘤细胞中的强表达,高表达与短期生存相关。这些发现表明,SLC11A1可作为CRC患者总生存的预测生物标志物。