We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprisingCCND1,ECT2,EpCAM,FSCN1,KRT5,KRT18,MET,TFRC,TWIST1, andVEGFC, was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples (n= 77) and clinicopathological features in ESCC patients (n= 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size (p= 0.031). The CTC-high patients were significantly correlated with advanced cancer stages (p= 0.013) and distant metastasis (p= 0.029). High mRNA levels ofTWIST1(Hazard Ratio (HR) = 5.44,p= 0.007),VEGFC(HR = 6.67,p< 0.001),TFRC(HR = 2.63,p= 0.034), andEpCAM(HR = 2.53,p= 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed thatTWIST1facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through theTWIST1-TGFBI-ZEB1axis in ESCC, highlighting the prognostic and therapeutic potential ofTWIST1in clinical ESCC treatment.
本研究通过检测与上皮-间质转化（EMT）相关的多个癌症驱动基因在转录水平的表达，探讨循环肿瘤细胞（CTCs）在癌症进展中的临床意义。我们建立了包含CCND1、ECT2、EpCAM、FSCN1、KRT5、KRT18、MET、TFRC、TWIST1和VEGFC的10基因检测组合，用于表征小鼠食管鳞癌（ESCC）异种移植模型及临床ESCC患者外周血（PB）样本中的CTCs。通过分析PB样本（n=77）中CTCs的基因表达与ESCC患者（n=55）临床病理特征的相关性，发现基线期CTCs的存在与肿瘤大小显著相关（p=0.031）。CTCs高表达患者与晚期癌症分期（p=0.013）及远处转移（p=0.029）显著相关。基线期TWIST1（风险比[HR]=5.44，p=0.007）、VEGFC（HR=6.67，p<0.001）、TFRC（HR=2.63，p=0.034）和EpCAM（HR=2.53，p=0.041）的高mRNA水平与ESCC患者较短的总生存期（OS）显著相关。本研究还揭示，在ESCC中TWIST1通过TWIST1-TGFBI-ZEB1轴促进肿瘤迁移、侵袭及顺铂化疗耐药，从而驱动EMT并增强恶性潜能，凸显了TWIST1在临床ESCC治疗中的预后价值及治疗潜力。
肿瘤(癌症)患者之家