RESUMEN
Timely and accurate diagnosis of Schistosoma infection is important to adopt effective strategies for schistosomiasis control. Previously, we demonstrated that Schistosoma japonicum can secret extracellular vesicles and their cargos may serve as a novel type of biomarkers for diagnosing schistosomiasis. Here, we developed a Gaussia luciferase immunoprecipitation assay combined with S. japonicum extracellular vesicle (SjEV) protein to evaluate its potential for diagnosing schistosomiasis. A saposin-like protein (SjSLP) identified from SjEVs was fused to the Gaussia luciferase as the diagnostic antigen. The developed method showed good capability for detecting S. japonicum infection in mice and human patients. We also observed that the method could detect Schistosoma infection in mice as early as 7 days of post-infection, which showed better sensitivity than that of indirect ELISA method. Overall, the developed method showed a good potential for detecting Schistosoma infection particularly for early stage, which may provide an alternative strategy for identify Schistosoma infection for disease control.
Asunto(s)
Inmunoprecipitación , Luciferasas , Schistosoma japonicum , Esquistosomiasis Japónica , Animales , Esquistosomiasis Japónica/diagnóstico , Esquistosomiasis Japónica/parasitología , Schistosoma japonicum/enzimología , Schistosoma japonicum/inmunología , Ratones , Humanos , Inmunoprecipitación/métodos , Luciferasas/genética , Femenino , Sensibilidad y Especificidad , Ratones Endogámicos BALB C , Ensayo de Inmunoadsorción Enzimática/métodos , Vesículas Extracelulares , Antígenos Helmínticos/análisis , Antígenos Helmínticos/inmunología , MasculinoRESUMEN
Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery.
Asunto(s)
Biomarcadores de Tumor , Vesículas Extracelulares , Neoplasias , Medicina de Precisión , Humanos , Vesículas Extracelulares/metabolismo , Medicina de Precisión/métodos , Biomarcadores de Tumor/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/genética , Neoplasias/diagnóstico , Animales , Microambiente Tumoral , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Extracellular vesicles (EVs) and EV proteins are promising biomarkers for cancer liquid biopsy. Herein, we designed a case-control study involving 100 controls and 100 patients with esophageal, stomach, colorectal, liver, or lung cancer to identify common and type-specific biomarkers of plasma-derived EV surface proteins for the five cancers. EV surface proteins were profiled using a sequencing-based proximity barcoding assay. In this study, five differentially expressed proteins (DEPs) and eight differentially expressed protein combinations (DEPCs) showed promising performance (area under curve, AUC > 0.900) in pan-cancer identification [e.g., TENM2 (AUC = 0.982), CD36 (AUC = 0.974), and CD36-ITGA1 (AUC = 0.971)]. Our classification model could properly discriminate between cancer patients and controls using DEPs (AUC = 0.981) or DEPCs (AUC = 0.965). When distinguishing one cancer from the other four, the accuracy of the classification model using DEPCs (85-92%) was higher than that using DEPs (78-84%). We validated the performance in an additional 14 cancer patients and 14 controls, and achieved an AUC value of 0.786 for DEPs and 0.622 for DEPCs, highlighting the necessity to recruit a larger cohort for further validation. When clustering EVs into subpopulations, we detected cluster-specific proteins highly expressed in immune-related tissues. In the context of colorectal cancer, we identified heterogeneous EV clusters enriched in cancer patients, correlating with tumor initiation and progression. These findings provide epidemiological and molecular evidence for the clinical application of EV proteins in cancer prediction, while also illuminating their functional roles in cancer physiopathology.