结肠癌患者淋巴结中干细胞标志物 EpCAM、LGR5 和 LGR4 mRNA 水平的临床意义。
Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients.
机构信息
Department of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, Sweden.
Department of Radiation Sciences, Oncology, Umeå University, SE-90185 Umeå, Sweden.
出版信息
Int J Mol Sci. 2021 Dec 30;23(1):403. doi: 10.3390/ijms23010403.
The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan-Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA copies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12-year follow-up ( = 0.022, = 0.005 and = 0.011, respectively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.
癌症干细胞（CSCs）在结肠癌（CC）的发生和进展中的意义已经确立。在这项研究中，我们研究了测量 CSC 标志物 EpCAM、LGR5 和 LGR4 的 mRNA 表达水平在预测接受手术治疗的 CC 患者生存结局中的应用价值。在 5 种 CC 细胞系、66 个原发性 CC 肿瘤和 121 名 CC 患者的 382 个区域淋巴结中测定了表达水平。使用 Kaplan-Meier 生存分析和 Cox 回归分析确定预后相关性。淋巴结中 EpCAM、LGR5 或 LGR4 表达水平较高（高于临床截值 0.07、0.06 和 2.558 mRNA 拷贝/18S rRNA 单位，分别）的 CC 患者，在 12 年的随访中，平均生存时间分别为 32 个月（EpCAM）和 42 个月（LGR5 和 LGR4）（=0.022、=0.005 和=0.011，分别）。当 LGR5 与生物标志物 CXCL17 或 CEA 加 CXCL16 联合使用时，还检测到了更多有复发风险的患者。总之，该研究强调了 LGR5 作为一种特别有用的预后生物标志物，并说明了结合检测不同癌细胞亚群和/或肿瘤微环境中细胞的生物标志物来预测复发的优势。
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