AGPAT家族成员作为宫颈癌潜在预测性生物标志物和治疗靶点的研究进展

Research Progress on AGPAT Family Members as Potential Predictive Biomarkers and Therapeutic Targets for Cervical Cancer

摘要: 宫颈癌是全球女性高发的恶性肿瘤之一，其早期诊断与精准治疗仍面临重要挑战。近年来，脂质代谢重编程被认为是肿瘤发生发展的关键特征，其中磷脂生物合成限速酶AGPAT (Acylglycerol-3-Phosphate O-Acyltransferase)家族的作用逐渐受到关注。AGPAT通过调控溶血磷脂酸向磷脂酸的转化，影响细胞膜脂质组成与结构重塑，并进而调节多条肿瘤相关信号通路的激活状态，在宫颈癌细胞增殖、侵袭、凋亡调控及代谢适应中发挥重要作用。现有研究显示，多数AGPAT家族成员在宫颈癌组织中呈异常表达，其中AGPAT2、AGPAT3的上调与肿瘤侵袭性增强及不良预后密切相关，而AGPAT6的下调可能与抑癌效应相关。此外，基于免疫组化、组织芯片、转录组及多组学分析的证据表明，AGPAT家族成员在宫颈癌的早期诊断、风险分层和预后评估中具有潜在应用价值。尽管针对AGPAT的靶向干预策略仍主要停留在基础与临床前研究阶段，但其作为代谢相关预测性生物标志物和潜在治疗靶点的生物学合理性已逐渐显现。文章系统综述AGPAT家族在宫颈癌中的表达特征、分子机制及其临床相关研究进展，为进一步探索宫颈癌的代谢干预策略和个体化治疗提供理论依据。

Abstract: Cervical cancer is one of the most prevalent malignant tumors among women worldwide, and its early diagnosis and precision treatment still face significant challenges. In recent years, lipid metabolic reprogramming has been recognized as a critical hallmark of cervical cancer progression, the role of the AGPAT (Acylglycerol-3-Phosphate O-Acyltransferase) family has garnered increasing attention—rate-limiting enzymes in phospholipid biosynthesis. AGPAT enzymes catalyze the conversion of lysophosphatidic acid to phosphatidic acid, subsequently modulating membrane lipid composition, membrane remodeling, and the activation of multiple oncogenic signaling pathways, thereby playing crucial roles in cervical cancer cell proliferation, invasion, apoptosis regulation, and metabolic adaptation. Recent studies have demonstrated aberrant expression patterns of AGPAT family members in cervical cancer, with upregulation of AGPAT2 and AGPAT3 closely associated with enhanced tumor aggressiveness and poor clinical outcomes, whereas downregulation of AGPAT6 may be linked to tumor-suppressive effects. Evidence derived from immunohistochemistry, tissue microarrays, transcriptomic profiling, and multi-omics analyses suggests that AGPAT family members hold potential application value in early diagnosis, risk stratification, and prognostic evaluation of cervical cancer. Although targeted therapeutic strategies against AGPAT remain primarily at the basic and preclinical research stages, the biological rationale for their utility as metabolism-related predictive biomarkers and potential therapeutic targets is gradually emerging. This review summarizes the expression patterns, molecular mechanisms, and clinical implications of AGPAT family members in cervical cancer, providing a theoretical basis for future metabolic intervention strategies and personalized therapeutic development.