射频消融（RFA）是结直肠癌肝转移局部治疗的重要方法之一，肝转移灶RFA治疗后残留肿瘤的转移严重影响患者预后，但其具体机制尚不明确。前期实验证明不全消融可促进小鼠结直肠癌肝转移灶残留肿瘤发生肺转移。通过转录组测序、生物信息学分析及预实验结果，我们提出射频消融后残留肿瘤细胞中SDPR/ERK/PPARγ信号轴介导的脂肪酸代谢重编程参与其肺转移的调控过程。本项目拟从细胞、动物水平及临床标本上探讨：（1）不全消融促进残留肿瘤细胞发生外源性脂肪酸摄取和β-氧化增强的脂肪酸代谢重编程，进而促使其肺转移；（2）SDPR在残留肿瘤细胞中高表达，通过抑制ERK磷酸化上调脂肪酸代谢关键转录因子PPARγ的表达，进而介导脂肪酸代谢重编程；（3）SDPR介导的脂肪酸代谢重编程促进残留肿瘤细胞的肺转移。旨在从代谢角度揭示结直肠癌肝转移灶不全消融后肿瘤进展的新机制，寻找潜在的治疗靶点和策略以提高RFA疗效。

Radiofrequency ablation (RFA) has become one of the important local treatment of colorectal liver metastases. However, the distant metastasis of residual tumor after RFA on liver metastases severely affect the prognosis of patients, the specific mechanism of which now is still unclear. In our previous study, we found that incomplete RFA on colorectal liver metastases in mice promoted distant lung metastasis of residual cancer. Based on the transcriptional sequencing, bioinformatics analysis, and preliminary experiments, we put forward that fatty acid metabolism reprogramming induced by SDPR/ERK/ PPARγ signaling axis in residual tumor cells after incomplete RFA might be involved in the regulation of lung metastasis. This study will explore at the levels of cell lines, mice and clinical samples, (1) incomplete RFA induces fatty acid metabolism reprogramming in residual tumor cells mediated by increased uptake of exogenous fatty acid and enhanced β-oxidation, and then promotes lung metastasis; (2) the highly expressed SDPR in residual tumor cells upregulates PPARγ, a key transcription factor in fatty acid metabolism, via inhibiting phosphorylation of ERK to induce fatty acid metabolism reprogramming; (3) fatty acid metabolism reprogramming induced by SDPR promotes lung metastasis of residual tumor cells. This study aims to reveal the new mechanism of residual tumor progression after RFA treatment of colorectal liver metastases in terms of cell metabolism, and provide potential targets and therapy strategy to improve RFA efficacy.