背景：结直肠癌肝转移是预后不良的主要风险因素，需要积极的干预和治疗。癌相关成纤维细胞（CAFs）在转移中起着关键作用，特别是代谢重编程方面。然而，对癌相关成纤维细胞代谢表型与免疫细胞之间关联的了解有限。本研究利用单细胞和批量转录组数据解码肝转移中与代谢相关的癌相关成纤维细胞亚型和免疫细胞的作用，开发了与结直肠癌肝转移相关的CAFs预后模型。方法：本研究使用了来自癌症基因组图谱和基因表达杂志的全面数据集，筛选出与肿瘤相关成纤维细胞代谢表型有关的特征。应用Cox回归和Lasso回归方法确定与肿瘤相关的成纤维细胞的预后基因，并基于成纤维细胞亚型基因分数构建模型。随后进行功能、免疫和临床分析。结果：该研究证明了癌相关成纤维细胞细胞的代谢异质性。发现代谢状态不同的癌相关成纤维细胞细胞与不同免疫细胞之间存在显著差异的通信。基于癌相关成纤维细胞基因签名分数的预后特征可用于确定结直肠癌肝转移患者的预后状态。高免疫活性和与肿瘤相关通路的富集在具有高癌相关成纤维细胞基因签名分数的样本中观察到。此外，癌相关成纤维细胞基因签名分数可实际指导选择更敏感的化疗药物。结论：我们的研究确定了与代谢亚型相关的癌相关成纤维细胞的预后标志。该标志在结直肠癌肝转移的精准治疗中具有良好的临床应用前景。版权所有 © 2023 武、禹、王、高、谢、张。

Background: Colorectal cancer liver metastasis is a major risk factor of poor outcomes, necessitating proactive interventions and treatments. Cancer-associated fibroblasts (CAFs) play essential roles in metastasis, with a focus on metabolic reprogramming. However, knowledge about associations between Cancer-associated fibroblasts metabolic phenotypes and immune cell is limited. This study uses single-cell and bulk transcriptomics data to decode roles of metabolism-related subtype of Cancer-associated fibroblasts and immune cells in liver metastasis, developing a CAF-related prognostic model for colorectal cancer liver metastases. Methods: In this study, Cancer-associated fibroblasts metabolism-related phenotypes were screened using comprehensive datasets from The Cancer Genome Atlas and gene expression omnibus (GEO). Cox regression and Lasso regression were applied to identify prognostic genes related to Cancer-associated fibroblasts, and a model was constructed based on the Cancer-associated fibroblasts subtype gene score. Subsequently, functional, immunological, and clinical analyses were performed. Results: The study demonstrated the metabotropic heterogeneity of Cancer-associated fibroblasts cells. Cancer-associated fibroblasts cells with varying metabolic states were found to exhibit significant differences in communications with different immune cells. Prognostic features based on Cancer-associated fibroblasts signature scores were found to be useful in determining the prognostic status of colorectal cancer patients with liver metastases. High immune activity and an enrichment of tumor-related pathways were observed in samples with high Cancer-associated fibroblasts signature scores. Furthermore, Cancer-associated fibroblasts signature score could be practical in guiding the selection of chemotherapeutic agents with higher sensitivity. Conclusion: Our study identified a prognostic signature linked to metabotropic subtype of Cancer-associated fibroblasts. This signature has promising clinical implications in precision therapy for colorectal cancer liver metastases.Copyright © 2023 Wu, Yu, Wang, Gao, Xie and Zhang.