野生型胃肠间质瘤的临床病理特征及研究进展
Clinicopathological Features and Research Progress of Wild-Type Gastrointestinal Stromal Tumors
DOI: 10.12677/acm.2026.1631133, PDF,   
作者: 马 超：重庆医科大学第四临床学院，重庆；聂 刚*：重庆医科大学附属大学城医院消化内科，重庆
关键词: 野生型胃肠间质瘤；分子分型；分子诊断；靶向治疗；精准诊疗；Wild-Type Gastrointestinal Stromal Tumor； Molecular Subtyping； Molecular Diagnosis； Targeted Therapy； Precision Diagnosis and Treatment
摘要: 本研究探讨野生型胃肠间质瘤(wt-GIST)的临床病理特征、分子分型、检测技术及治疗进展，为其精准诊疗提供参考。胃肠间质瘤(GIST)中10%~15%为无c-KIT/血小板源性生长因子受体α (PDGFRA)经典基因突变的wt-GIST，其分子机制、临床表型及治疗响应与突变型GIST差异显著。二代测序(NGS)推动了wt-GIST分子分型体系的完善，该肿瘤以SDHB免疫组化(IHC)为核心分为SDH缺陷型和SDH功能正常型，前者因SDH复合体功能丧失引发代谢重编程与表观遗传修饰异常，后者则以RAS-MAPK等经典信号通路异常激活为主要驱动机制。手术是局限性wt-GIST的根治核心，SDH缺陷型不推荐常规淋巴结清扫，传统酪氨酸激酶抑制剂(TKI)疗效有限，奥雷巴替尼等新型靶向药在SDH缺陷型中展现突破性疗效，免疫联合治疗及CD36代谢靶向治疗为新方向。目前wt-GIST仍存在诊疗策略不完善、部分亚型缺乏有效治疗手段等瓶颈，未来需依托多组学技术深化研究，完善精准诊疗体系。
Abstract: This study investigated the clinicopathological features, molecular subtyping, detection technologies and treatment progress of wild-type gastrointestinal stromal tumors (wt-GIST) to provide a reference for its precision diagnosis and treatment. Approximately 10% to 15% of gastrointestinal stromal tumors (GISTs) are wt-GISTs without classic c-KIT/platelet-derived growth factor receptor α (PDGFRA) gene mutations, which exhibit distinct molecular mechanisms, clinical phenotypes and treatment responses compared with mutant GISTs. Next-Generation Sequencing (NGS) has promoted the improvement of the molecular subtyping system for wt-GISTs. Based on succinate dehydrogenase B (SDHB) immunohistochemistry (IHC), wt-GISTs are classified into two major subtypes: SDH-deficient and SDH-proficient. The former is driven by metabolic reprogramming and aberrant epigenetic modifications caused by loss of SDH complex function, whereas the latter is mainly characterized by abnormal activation of classic signaling pathways such as RAS-MAPK. Surgical resection is the cornerstone of curative therapy for localized wt-GISTs, and routine lymph node dissection is not recommended for SDH-deficient subtypes. Conventional tyrosine kinase inhibitors (TKIs) show limited therapeutic efficacy, while novel targeted agents such as olverembatinib have demonstrated groundbreaking efficacy in the treatment of SDH-deficient wt-GISTs. Immune combination therapy and CD36-mediated metabolic targeted therapy have emerged as promising new therapeutic directions. At present, the clinical management of wt-GISTs still faces bottlenecks including incomplete diagnosis and treatment strategies and the lack of effective therapeutic approaches for some subtypes. In the future, it is necessary to conduct in-depth research relying on multi-omics technologies and further improve the precision diagnosis and treatment system for wt-GISTs.
文章引用：马超, 聂刚. 野生型胃肠间质瘤的临床病理特征及研究进展[J]. 临床医学进展, 2026, 16(3): 3272-3281. https://doi.org/10.12677/acm.2026.1631133

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