Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer

Abstract

Background Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. Methods Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. Results Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. Conclusions These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

Exosomal Proteomics: Unveiling Novel Insights into Lung Cancer

“…Further enriching the diagnostic toolkit, Jin et al's study on urine exosomes identified differential expression of WASL, STK10, and WNK1 as potential lung cancer biomarkers [177]. These findings, along with the identification of FGB, FGG, and VWF in exosome panels, fortify the prospect of early NSCLC diagnosis and shed light on the correlation of survival duration, emphasizing the significance of exosomal proteins in lung cancer prognosis [178].…”

“…Moreover, the identification of CFHR5, C9, and MBL2 as biomarkers for NSCLC metastasis assessment, along with interleukin-34, HLA-DMA, and HLA-DOB in serum exosomes, underscores the intricate role of exosomal proteins in NSCLC progression and immune system interactions [178,179]. This finding is complemented by the correlation of FAM166B, Killer Cell Immunoglobulin-like Receptor 2DL1, and Olfactory Receptor 52R1 with lymph node metastasis, providing a prognostic perspective on NSCLC metastatic spread [179].…”