bims-exocan 2024-04-28 papers

Issue of 2024‒04‒28
five papers selected by
Muhammad Rizwan, COMSATS University

Mil Med Res. 2024 Apr 22. 11(1): 24

Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction.

Ting Gong, You-Tan Liu, Jie Fan.

Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.

Keywords: Biomarkers; Exosomes; Inflammation; Intercellular crosstalk; Sepsis

DOI: https://doi.org/10.1186/s40779-024-00527-6

Front Oncol. 2024 ;14 1334592

Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Jianjun Wang, Ruizi Shi, Yuan Yin, Hua Luo, Yuan Cao, Yun Lyu, Huiwen Luo, Xintao Zeng, Decai Wang.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Keywords: biomarker; cholangiocarcinoma; exosome; extracellular vesicles; liquid biopsy; microparticle

DOI: https://doi.org/10.3389/fonc.2024.1334592

Heliyon. 2024 Apr 30. 10(8): e29551

Identification of exosome-related gene signature as a promising diagnostic and therapeutic tool for breast cancer.

Qitong Chen, Qin Zhou.

Background: Exosomes are promising tools for the development of new diagnostic and therapeutic approaches. Exosomes possess the ability to activate signaling pathways that contribute to the remodeling of the tumor microenvironment, angiogenesis, and the regulation of immune responses. We aimed to develop a prognostic score based on exosomes derived from breast cancer.Materials and methods: Training was conducted on the TCGA-BRCA dataset, while validation was conducted on GSE20685, GSE5764, GSE7904, and GSE29431. A total of 121 genes related to exosomes were retrieved from the ExoBCD database. The Cox proportional hazards model is used to develop risk score model. The GSVA package was utilized to analyze single-sample gene sets and identify exosome signatures, while the WGCNA package was utilized to identify gene modules associated with clinical outcomes. The clusterProfiler and GSVA R packages facilitated gene set enrichment and variation analyses. Furthermore, CIBERSORT quantified immune infiltration, and a correlation between gene expression and drug sensitivity was assessed using the TIDE algorithm.
Results: An exosome-related prognostic score was established using the following selected genes: ABCC9, PIGR, CXCL13, DOK7, CD24, and IVL. Various immune cells that promote cancer immune evasion were associated with a high-risk prognostic score, which was an independent predictor of outcome. High-risk and low-risk groups exhibited significantly different infiltration abundances (p < 0.05). By conducting a sensitivity comparison, we found that patients with high-risk scores exhibited more favorable responses to immunotherapy than those with low-risk scores.
Conclusion: The exosome-related gene signature exhibits outstanding performance in predicting the prognosis and cancer status of patients with breast cancer and guiding immunotherapy.

Keywords: Breast cancer; Exosome; Immunotherapy; Prognostic score; Tumor microenvironment

DOI: https://doi.org/10.1016/j.heliyon.2024.e29551

Cancers (Basel). 2024 Apr 12. pii: 1482. [Epub ahead of print]16(8):

Patient-Derived Exosomes as siRNA Carriers in Ovarian Cancer Treatment.

Aasa Shimizu, Kenjiro Sawada, Masaki Kobayashi, Yukako Oi, Tadashi Oride, Yasuto Kinose, Michiko Kodama, Kae Hashimoto, Tadashi Kimura.

RNA interference is a powerful gene-silencing tool with potential clinical applications. However, its therapeutic use is challenging because suitable carriers are unavailable. Exosomes are stable small endogenous vesicles that can transport functional molecules to target cells, making them ideal small interfering RNA (siRNA) carriers. Herein, we elucidated the therapeutic potential of patient-derived exosomes as an siRNA carrier for ovarian cancer (OC) treatment. The exosomes were extracted from the culture medium of primary fibroblasts collected from the omentum of patients with OC during surgery. MET proto-oncogene, receptor tyrosine kinase (MET) was selected for gene silencing, c-Met siRNAs were synthesized and loaded into the exosomes (Met-siExosomes) via electroporation, and the treatment effect of the Met-siExosomes was assessed in vitro and in vivo. The Met-siExosomes downregulated the c-Met protein levels and inhibited OC cell proliferation, migration, and invasion. In xenograft experiments using SKOV3-13 and ES-2 cells, Met-siExosomes were selectively extracted from peritoneally disseminated tumors. Intraperitoneal treatment suppressed the c-Met downstream targets in cancer cells and prolonged mouse survival. The synthesized siRNAs were successfully and selectively delivered via the exosomes to intraperitoneally disseminated tumors. As patients with OC routinely undergo omentectomy and abundant fibroblasts can be easily collected from the omentum, patient-derived exosomes may represent a promising therapeutic siRNA carrier to treat OC.

Keywords: MET; exosomes; fibroblasts; omentum; ovarian cancer; peritoneal dissemination; siRNAs

DOI: https://doi.org/10.3390/cancers16081482

Crit Rev Anal Chem. 2024 Apr 26. 1-12

Exosome, a Rising Biomarkers in Liquid Biopsy: Advances of Label-Free and Label Strategy for Diagnosis of Cancer.

Qian Liu, Jing Zheng, An Xie, Min Chen, Rui-Yue Gong, Yuan Sheng, Hong-Lei Chen, Chu-Bo Qi.

Cancer is commonly considered as one of the most severe diseases, posing a significant threat to human health and society due to various serious challenges. These challenges include difficulties in accurate diagnosis and a high propensity to form metastasis. Tissue biopsy remains the gold standard for diagnosing and subtyping cancer. However, concerns arise from its invasive nature and the potential risk of metastasis during these complex diagnostic procedures. Meanwhile, liquid biopsy has recently witnessed the rapid advancements with the emergence of three prominent detection biomarkers: circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Whereas, the very low abundance of CTCs combined with the instability of ctDNA intensify the challenges and decrease the accuracy of these two biomarkers for cancer diagnosis. While exosomes have gained widespread recognition as a promising biomarker in liquid biopsy due to their relatively low-invasive detection method, excellent biostability, rich resources, high abundance, and ability to provide valuable information about cancer. Therefore, it is crucial to systematically summarize recent advancements mainly in exosome-based detection methods for early cancer diagnosis. Specifically, this review will primarily focus on label-based and label-free strategies for detecting cancer using exosomes. We anticipate that this comprehensive analysis will enhance readers' understanding of the significance and value of exosomes in the fields of cancer diagnosis and therapy.

Keywords: Cancer diagnosis; circulating tumor DNA; circulating tumor cells; exosomes; liquid biopsy

DOI: https://doi.org/10.1080/10408347.2024.2339961