bims-exocan 2024-07-21 papers

Issue of 2024–07–21
two papers selected by
Muhammad Rizwan, COMSATS University

Clin Transl Oncol. 2024 Jul 17.

The diagnostic value of serum exosomal SNORD116 and SNORA21 for NSCLC patients.

Lin Li, Zhijun Zhang, Wei Xu, Jun Wang, Xiaodong Feng.

PURPOSE: Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC.
METHODS: Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance.
RESULTS: In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784.
CONCLUSION: This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC.

Keywords: Biomarkers; Exosomes; Metastasis; NSCLC; snoRNAs

DOI: https://doi.org/10.1007/s12094-024-03606-1

Elife. 2024 Jul 15. pii: RP95191. [Epub ahead of print]13

Emerging role of oncogenic ß-catenin in exosome biogenesis as a driver of immune escape in hepatocellular carcinoma.

Camille Dantzer, Justine Vaché, Aude Brunel, Isabelle Mahouche, Anne-Aurélie Raymond, Jean-William Dupuy, Melina Petrel, Paulette Bioulac-Sage, David Perrais, Nathalie Dugot-Senant, Mireille Verdier, Barbara Bessette, Clotilde Billottet, Violaine Moreau.

Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A, two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.

Keywords: cancer; cancer biology; cell biology; exosomes; extracellular vesicles; human; liver; ß-catenin

DOI: https://doi.org/10.7554/eLife.95191