背景:循环肿瘤细胞(CTC)在肿瘤转移中至关重要,然而它们在肾癌中的具体作用尚不清楚.
方法:本研究利用生物信息学研究了C-C基序趋化因子配体5(CCL5)对肾癌细胞和CTC的致瘤影响,在体内,和体外实验。它还通过Lasso回归和Kaplan-Meier存活曲线评估肾癌患者CTC的预后价值。
结果:生物信息学分析揭示了关注CTC和肿瘤细胞之间的细胞粘附和迁移的差异基因。CCL5在各种CTC中表现出高表达,与肾癌预后不良有关。在786-O-CTC中,CCL5增强恶性肿瘤,而在肾细胞癌细胞系CAKI-2和786-O中,它通过smad2/3促进上皮-间质转化(EMT),影响细胞特性。裸鼠模型提示CCL5增加CTC和增强EMT,增强肺转移。临床结果显示不同EMT型CTC的预后值不同,间充质CTC具有最高的价值。
结论:总之,CCL5通过smad2/3促进肾癌细胞和CTC的EMT,增强恶性表型并促进肺转移。间充质型CTC相关因子可构建肾癌患者的风险模型,允许基于转移风险预测的个性化治疗。
BACKGROUND: Circulating tumor cells (
CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear.
METHODS: This study investigated C-C motif chemokine ligand 5 (CCL5)\'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients\' CTCs prognostic value through Lasso regression and Kaplan-Meier survival curves.
RESULTS: Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various
CTCs, correlating with poor prognosis in renal cancer. In 786-O-
CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased
CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed
CTCs, with mesenchymal
CTCs having the highest value.
CONCLUSIONS: In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.