结直肠癌进展中的ERO1A阳性瘤上皮细胞:一个多omics视角
Shangshang Hu1,2, Jinwei Lou3, Yuhan Chen3
1School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
Apoptosis : an international journal on programmed cell death
|October 1, 2025
概括
研究人员确定了驱动结直肠癌 (CRC) 进展和转移的ERO1A阳性上皮细胞 (ERO1A+Epi). 一个新的风险评分,ETSRM,利用这些细胞显示改善了CRC患者的预后准确性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 结肠直肠癌 (CRC) 是一个主要的全球健康问题,瘤上皮细胞显著影响瘤微环境 (TME) 和癌症的进展.
- 了解TME内部的特定细胞组件和相互作用对于开发有效的治疗策略至关重要.
研究的目的:
- 为了确定涉及结直肠癌进展的新型上皮细胞亚群.
- 阐明这些子群体在塑造瘤微环境中的作用及其对患者预后的影响.
- 根据已识别的细胞驱动因素,开发一种新的结直肠癌预后模型.
主要方法:
- 综合单细胞转录组学,批量转录组学,空间转录组学和来自21个队伍的2,767名CRC患者的蛋白质组学.
- 在体外和体外实验,用于对已识别的细胞群和细胞通路进行功能验证.
- 生物信息分析包括空间和细胞间相互作用分析,以映射TME动态.
- 基于已识别的上皮细胞标记物和TME评分的风险预测模型 (ETSRM) 的开发和验证.
主要成果:
- 一个独特的上皮细胞亚群,ERO1A阳性上皮细胞 (ERO1A+Epi),被确定并发现富含于晚期CRC,与预后不佳相关.
- 在体外,ERO1A+Epi细胞促进了癌细胞的增殖,迁移,入侵和上皮-介质细胞过渡 (EMT),并在体内增强了瘤生长和肝转移.
- ERO1A+Epi细胞通过特定的信号通路 (MDK-LRP1,MIF-(CD74+CD44),APP-CD74) 与癌症相关纤维细胞 (CAF) 和巨细胞相互作用,促进一种亲瘤的TME.
- 基于ERO1A+Epi_TME_Score开发的ETSRM模型,与现有的111个CRC模型相比,显示出更高的预测准确性,与TNM分期集成后进一步改善.
结论:
- 已确定ERO1A+Epi细胞是结直肠癌进展和转移的重要驱动因素.
- ETSRM模型为CRC提供了强大的预后工具,提高了生存预测的准确性.
- 这些发现为CRC病变产生提供了新的见解,并突出了ERO1A+Epi细胞及其相互作用作为改善患者结果的潜在治疗点.
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