Comparative proteomic profiling of plasma exosomes in lung cancer cases of liver and brain metastasis

Abstract

Background Metastases within liver or the brain are the most common causes of mortality from lung cancer (LC). Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging but important for early patient intervention. According to mounting evidence, exosomes circulating within blood may facilitate cancer spread by transporting certain proteins for target cells. Methods Using liquid chromatography–MS/MS, we investigated the plasma exosomes’ proteomic profiles derived from 42 metastatic LC patients [16 solitary liver metastasis (LM), together with 26 solitary brain metastasis (BM)] and 25 local advanced (LA) lung cancer cases without metastasis, together with five healthy controls (HC), assessing the LM and BM pathogenesis and find potential novel organ-designated proteomic biomarkers. Using ELISA assay, we verified the expression levels of three plasma exosomal protein biomarkers in 110 LC patients, including 40 solitary LM, 32 solitary BM and 38 LA, and 25 HC. Results In total, 143 and 120 differentially expressed exosome-based proteins (DEEPs) were found to be dysregulated in LM and BM of lung cancer (LM-DEEPs, BM-DEEPs), compared for LA lung cancer samples, respectively. The bioinformatics analyses indicated the heterogeneity and homogeneity in LM-DEEPs and BM-DEEPs. They were primarily engaged within proteomic triggering cascade, ECM-receptor interaction, and the collagen-containing extracellular matrix. Regarding heterogeneity, LM-DEEPs primarily consisted of proteoglycans, lipoprotein, integrin, and heat shock protein, whereas the BM-DEEPs consisted of calcium-dependent/S100 proteins. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)-plasma-stemming exosome proteomics showed heterogeneity, which helped to explain some of the differences between SCLC and NSCLC's metastatic features. We also found that SELL and MUC5B could be used as diagnostic markers of BM, while APOH, CD81, and CCT5 could help diagnose LM in LC patients. Additionally, we demonstrated in a validation cohort that MUC5B and SELL could serve as biomarkers for diagnosing BM, and APOH could be a novel potential diagnostic biomarker of LM. Conclusion We presented the comprehensive and comparative plasma-stemming exosomes’ proteomic profiles from cases of LC who had isolated liver and brain metastases for the first time. We also suggested several possible biomarkers and pathogenic pathways that might be a great starting point for future research on LC metastasis.

Characterization of effective, simple, and low‐cost precipitation methods for depleting abundant plasma proteins to enhance the depth and breadth of plasma proteomics

“…An emerging and important source of potential blood biomarkers are exosomes, which are small membrane-bound organelles secreted by cells that can contain nucleic acids or other cellular components [22][23][24][25][26]. Our comparison of cellular components associated with enriched proteins derived from the various plasma protein precipitation methods reveals consistent similarities and differences between acid-and solvent-based approaches.…”

Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model

“…In this study, mesenchymal stem cell exosomes were extracted from mouse bone marrow, with a focus on their crucial role as intercellular communicators carrying bioactive molecules that influence the behavior of recipient cells [ 25 – 27 ]. Through meticulous characterization via Transmission TEM and NTA, the exosomes’ size and morphology were confirmed, aligning with established exosomal profiles [ 28 ]. This verification is essential, underpinning the therapeutic implications of the findings within the broader scope of PCOS treatment.…”

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

“…Profiling the proteins within exosomes allows for precise differentiation between tumorous and normal cells, with multi-panel profiling demonstrating effectiveness in predicting tumor origin [117]. Exosomes enriched with specific proteins can condition the brain microenvironment to facilitate cancer cell proliferation, as evidenced by the elevated colonization and invasiveness observed in brain tissues treated with exosomes derived from brain metastatic cells [118].…”