ALDH1A1、ALDH1A3与胃癌发生发展关系的研究综述——表达特征、预后价值及二者协同作用研究现状

A Review of the Relationship between ALDH1A1, ALDH1A3 and the Occurrence and Progression of Gastric Cancer—Research Status of Expression Characteristics, Prognostic Value and Their Synergistic Effect

摘要: 乙醛脱氢酶(ALDH)家族是调控细胞醛代谢、氧化还原稳态的关键酶系，其中ALDH1A1、ALDH1A3作为核心肿瘤干细胞标志物，在胃癌等恶性肿瘤发生发展中发挥核心作用。本文系统梳理ALDH家族整体生物学功能，分别阐述ALDH1A1、ALDH1A3在多类实体肿瘤中的表达特征、分子机制与临床价值：ALDH1A1高表达与胃癌肿瘤分期、分化程度、淋巴结转移及化疗耐药密切相关，可独立评估患者预后，通过调控氧化还原平衡、Notch通路促进肿瘤增殖侵袭；ALDH1A3参与肿瘤代谢重编程，介导5-氟尿嘧啶等药物耐受，调控肿瘤相关巨噬细胞极化参与免疫逃逸。二者存在代谢层面协同调控关系，联合高表达会强化胃癌干细胞干性、侵袭转移与治疗抵抗，具备联合诊断与联合靶向干预潜力。现有研究仍存在短板：二者在胃癌中完整分子通路未完全解析、相互协同作用机制缺乏系统验证，相关机制研究较为匮乏。深入挖掘ALDH1A1、ALDH1A3在胃癌中的交互调控网络，能够为胃癌早期筛查、预后评估及新型联合靶向治疗提供理论依据。

Abstract: The aldehyde dehydrogenase (ALDH) family is a key enzyme system regulating cellular aldehyde metabolism and redox homeostasis. As core markers of cancer stem cells, ALDH1A1 and ALDH1A3 exert vital functions in the initiation and progression of malignant tumors including gastric cancer. This paper systematically reviews the overall biological functions of the ALDH family, and elaborates on the expression profiles, molecular mechanisms and clinical values of ALDH1A1 and ALDH1A3 in various solid tumors respectively. High expression of ALDH1A1 is closely correlated with tumor stage, differentiation, lymph node metastasis and chemoresistance in gastric cancer, which serves as an independent prognostic factor and facilitates tumor proliferation and invasion by modulating redox balance and Notch signaling pathway. ALDH1A3 participates in tumor metabolic reprogramming, mediates tolerance to chemotherapeutic agents such as 5-fluorouracil, and regulates the polarization of tumor-associated macrophages to induce immune escape. ALDH1A1 and ALDH1A3 exert synergistic regulatory effects at the metabolic level; their concurrent overexpression strengthens stemness, invasion, metastasis and therapeutic resistance of gastric cancer cells, showing great potential for combined diagnosis and combinatorial targeted therapy. Current researches still have limitations: the complete molecular pathways of the two genes in gastric cancer have not been fully clarified, and systematic verification of their synergistic mechanisms is insufficient. Further exploration of the interactive regulatory network between ALDH1A1 and ALDH1A3 in gastric cancer can provide theoretical basis for early screening, prognostic evaluation and novel combinatorial targeted therapy of gastric cancer.