Posgrado en Ciencias Biológicas, Unidad de Posgrado, Edificio A, 1° Piso, Circuito de Posgrados, Ciudad Universitaria, C.P. 04510, Coyoacán, Distrito Federal, Mexico.
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Seccion XVI, Tlalpan, 14080, Mexico City, Mexico.
Stem Cell Res Ther. 2023 Feb 3;14(1):16. doi: 10.1186/s13287-023-03241-7.
Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Specific and thorough identification of cancer cell subsets with higher tumorigenicity and chemoresistance, such as cancer stem cells (CSCs), could lead to the development of new and promising therapeutic targets. For better CSC identification, a complete or extended surface marker phenotype is needed to provide increased specificity for new cell targeting approaches. Our goal is to identify and characterize a putative extended phenotype for CSCs derived from patients with GC before treatment, as well as to evaluate its clinical value. In addition, we aim to ensure that cells with this phenotype have stemness and self-renewal capabilities.
This is a cohort study including 127 treatment-naïve patients with GC who attended the Instituto Nacional de Cancerología. Multiparametric flow cytometry analysis was performed to determine the extended phenotype of cells derived from gastric biopsies. The tumorigenic capability of cells identified in patients was assessed in a zebrafish model.
CD24+CD44+CD54+EpCAM+ cells were present in all treatment-naïve patients included, with a median abundance of 1.16% (0.57-1.89%). The percentage of CD24+CD44+CD54+EpCAM+ cells was categorized as high or low using 1.19% as the cutoff for the CD24+CD44+CD54+EpCAM+ cell subset. Additionally, a higher TNM stage correlated with a higher percentage of CD24+CD44+CD54+EpCAM+ cells (Rho coefficient 0.369; p < 0.0001). We also demonstrated that a higher percentage of CD24+CD44+CD54+EpCAM+ cells was positively associated with metastasis. The metastatic potential of these cells was confirmed in a zebrafish model. Ultimately, under our conditions, we conclude that CD24+CD44+CD54+EpCAM+ cells are true gastric cancer stem cells (GCSCs).
The CD24+CD44+CD54+EpCAM+ cells present in tissue samples from patients are true GCSCs. This extended phenotype results in better and more specific characterization of these highly tumorigenic cells. The relative quantification of CD24+CD44+CD54+EpCAM+ cells has potential clinical value, as these cells are associated with metastatic disease, making their presence an additional prognostic marker and possibly a target for the design of new antineoplastic treatments in the era of precision oncology. Overall, the extended CD24+CD44+CD54+EpCAM+ phenotype of GCSCs could support their isolation for the study of their stemness mechanisms, leading to the identification of better molecular targets for the development of both new therapeutic approaches such as oncoimmunotherapy and new diagnostic and clinical prognostic strategies for GC.
胃癌（GC）是全球癌症相关死亡的主要原因。特异性和彻底地识别具有更高致瘤性和化疗耐药性的癌细胞亚群，如癌症干细胞（CSC），可能会为新的有前途的治疗靶点的开发提供依据。为了更好地识别 CSC，需要完整或扩展的表面标记表型，以提供针对新细胞靶向方法的更高特异性。我们的目标是鉴定和表征治疗前来自 GC 患者的 CSC 的假定扩展表型，并评估其临床价值。此外，我们旨在确保具有这种表型的细胞具有干细胞特性和自我更新能力。
这是一项队列研究，纳入了 127 名接受治疗的 GC 患者，这些患者均来自国立癌症研究所。使用多参数流式细胞术分析确定来自胃活检的细胞的扩展表型。通过斑马鱼模型评估在患者中鉴定的细胞的致瘤能力。
所有纳入的治疗前患者均存在 CD24+CD44+CD54+EpCAM+细胞，中位数丰度为 1.16%（0.57-1.89%）。使用 1.19%作为 CD24+CD44+CD54+EpCAM+细胞亚群的截止值，将 CD24+CD44+CD54+EpCAM+细胞的百分比分为高或低。此外，较高的 TNM 分期与较高的 CD24+CD44+CD54+EpCAM+细胞百分比相关（Rho 系数 0.369；p<0.0001）。我们还表明，较高的 CD24+CD44+CD54+EpCAM+细胞百分比与转移呈正相关。这些细胞的转移潜力在斑马鱼模型中得到了证实。最终，根据我们的条件，我们得出结论，CD24+CD44+CD54+EpCAM+细胞是真正的胃癌干细胞（GCSC）。
来自患者组织样本中的 CD24+CD44+CD54+EpCAM+细胞是真正的 GCSC。这种扩展表型可更好地、更具体地对这些高度致瘤性细胞进行特征描述。CD24+CD44+CD54+EpCAM+细胞的相对定量具有潜在的临床价值，因为这些细胞与转移性疾病相关，使其成为额外的预后标志物，并可能成为精准肿瘤学时代新抗肿瘤治疗设计的靶点。总体而言，GCSC 的扩展 CD24+CD44+CD54+EpCAM+表型可支持其分离以研究其干细胞机制，从而为开发新的治疗方法（如肿瘤免疫治疗）和新的诊断及临床预后策略提供更好的分子靶点。
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