Alveolar echinococcosis (AE) is a lethal zoonotic disease caused by the Echinococcus multilocularis metacestode in animals and humans [1,2]. Humans are infected through accidental ingestion of parasitic eggs from definitive host feces. This disease poses a significant health concern, causing significant morbidity and economic losses, particularly in rural areas of China such as Xinjiang, Ningxia, Qinghai, and Gansu [3]. In the early stages, patients of AE disease may be asymptomatic, but if left untreated, 90 % of cases can prove fatal within 10 to 15 years post-diagnosis. The feasibility of surgery options and/or chemotherapy in the treatment of AE depends on a wide range of factors such as characteristics of the location and size of the metacestode lesion [4]. If surgery is performed, it is always accompanied by chemoprophylaxis with benzimidazoles [5,6]. However, administration of these compounds is often associated with adverse side effects, and currently, there are no alternative drugs available for AE patients who experience severe side effects [7,8]. Moreover, benzimidazole therapy itself also has notable limitations, including its parasitostatic nature, limited efficacy, and side effects [6,9].

The liver is the most common target for the parasite, where E. multilocularis metacestodes are growing slowly, leading to chronic progressive hepatic damage and prolonged infection [10]. The variability in E. multilocularis metacestode development across different hosts and tissues is notable, with some forming fertile cysts rich in protoscoleces (PSCs), while others remain largely infertile [[11], [12], [13]]. Two types of E. multilocularis metacestodes are observed across intermediate hosts: one type of metacestodes containing viable PSCs attached to the germinal layer and free in the cyst flu id, and the other type containing few or no PSCs [14]. The immune factors established by the different intermediate hosts result in distinct resistance to E. multilocularis [15]. In experimental rodents, the impairment of immune response is associated with increased susceptibility to E. multilocularis [15,16]. Conversely, the frequent absence of PSCs in humans suggests that they may possess a relatively higher resistance to E. multilocularis infection [11,15]. Previous studies have found fewer PSCs in the subcutaneous cysts (SCs) compared to those in intraperitoneal cysts (ICs) [17]. However, the mechanism underlying the generation of E. multilocularis metacestodes in different tissues remains unclear. This study aims to explore the proteomic distinctions between SCs and ICs to better understand the occurrence and development of metacestodes.