结直肠癌中ACOX1高表达预示着临床预后良好

High Expression of ACOX1 in Colorectal Cancer (CRC) Predicting a Favorable Clinical Prognosis

摘要: 目的：结直肠癌(CRC)患者预后不良，现仍需要探索新的分子靶点以更准确地进行预后评估及药物治疗。能量代谢异常被认为是癌症进展过程中的一大重要环节，其中脂质代谢失调已被证明参与癌细胞的发生发展。酰基辅酶A氧化酶1 (ACOX1)是参与脂质代谢调节的一种关键酶，很少有报道揭示其对CRC的影响。在本研究中，我们通过TCGA数据库评估了ACOX1基因在CRC中的作用。方法：利用GEPIA分析CRC中ACOX1基因的表达情况。通过生存模块评估ACOX1基因对CRC患者生存的影响。然后，从TCGA下载CRC数据集。使用逻辑回归分析临床信息与ACOX1基因表达之间的相关性。使用Cox回归分析识别与患者总体生存相关的临床病理特征。结果：逻辑回归分析中，ACOX1表达作为分类的因变量，表明ACOX1表达增加与病理分期、肿瘤原发灶状态和区域淋巴结受累情况显著相关。此外，单因素Cox回归分析表明，局部淋巴结受累、远处转移情况、年龄、癌胚抗原水平、淋巴侵袭情况、ACOX1高表达与CRC患者的总体生存率显著相关。结论：本研究基于TCGA数据库探讨酰基辅酶A氧化酶1 (ACOX1)在结直肠癌(CRC)中的表达特征及预后价值。结果显示，ACOX1在正常结肠组织中的表达显著高于肿瘤组织(P < 0.001)，其高表达与患者总体生存率(HR = 0.60, P = 0.003)、疾病特异性生存率(HR = 0.54, P = 0.007)及无进展间隔期(HR = 0.72, P = 0.038)改善显著相关，提示ACOX1可能通过调控脂质代谢抑制肿瘤进展。多因素分析表明，ACOX1的独立预后价值受病理分期及癌胚抗原水平等混杂因素影响(HR = 0.379, P = 0.080)，暗示其作用依赖于代谢网络复杂性。机制上，ACOX1可能通过过氧化物酶体β-氧化调节脂肪酸代谢，影响活性氧生成及表观遗传修饰，进而调控肿瘤恶性表型。ROC曲线显示基于ACOX1的预后模型区分效能显著(AUC = 0.876)，具有临床转化潜力。研究局限性包括回顾性数据偏差及机制未完全阐明。本研究为CRC代谢靶向治疗提供了新视角，强调ACOX1在肿瘤脂质重编程中的潜在作用。

Abstract: Objective: Colorectal cancer (CRC) patients exhibit poor prognosis, and the exploration of novel molecular targets remains crucial for more accurate prognostic assessment and drug therapy. Abnormal energy metabolism has been recognized as a significant component in cancer progression, with lipid metabolism dysregulation demonstrated to contribute to carcinogenesis and cancer development. Acyl-CoA oxidase 1 (ACOX1), a key enzyme involved in lipid metabolism regulation, has rarely been reported regarding its impact on CRC. In this study, we investigated the role of the ACOX1 gene in CRC using data from the Cancer Genome Atlas (TCGA) database. Methods: The expression profile of ACOX1 in CRC was analyzed using GEPIA. The survival module was employed to evaluate the impact of ACOX1 on CRC patient survival. Subsequently, the CRC dataset was downloaded from TCGA. Logistic regression analysis was performed to assess correlations between clinical parameters and ACOX1 expression. Cox regression analysis was conducted to identify clinicopathological characteristics associated with overall survival. Results: In logistic regression analysis with ACOX1 expression as a categorical dependent variable, elevated ACOX1 expression showed significant correlations with pathological stage, primary tumor status, and regional lymph node involvement. Furthermore, univariate Cox regression analysis revealed that local lymph node metastasis, distant metastasis status, age, carcinoembryonic antigen (CEA) level, lymphatic invasion, and high ACOX1 expression were significantly associated with overall survival in CRC patients. Conclusion: This study investigated the expression characteristics and prognostic value of acyl-CoA oxidase 1 (ACOX1) in colorectal cancer (CRC) using the TCGA database. Key findings demonstrated that ACOX1 expression was significantly higher in normal colon tissues than in tumor tissues (P < 0.001). Elevated ACOX1 expression correlated with improved overall survival (HR = 0.60, P = 0.003), disease-specific survival (HR = 0.54, P = 0.007), and progression-free interval (HR = 0.72, P = 0.038), suggesting its potential tumor-suppressive role through lipid metabolism regulation. Multivariate analysis indicated that ACOX1’s independent prognostic value was influenced by confounding factors including pathological stage and carcinoembryonic antigen levels (HR = 0.379, P = 0.080), implying context-dependent effects within metabolic networks. Mechanistically, ACOX1 may modulate fatty acid metabolism via peroxisomal β-oxidation, subsequently influencing reactive oxygen species generation and epigenetic modifications to regulate malignant phenotypes. The ACOX1-based prognostic model demonstrated significant discriminative power (AUC = 0.876) in ROC analysis, highlighting clinical translation potential. Limitations include retrospective data bias and incomplete mechanistic elucidation. This work provides novel insights into metabolic targeting for CRC, emphasizing ACOX1’s role in tumor lipid reprogramming.