Harnessing Serum Exosomal snoRNAs: A Novel Liquid Biopsy Approach for NSCLC Diagnosis.

BACKGROUND The low early diagnostic efficacy of non-small cell lung cancer (NSCLC) is a key contributor to its high mortality rate, and small nucleolar RNAs (snoRNAs) in serum exosomes can serve as a beneficial liquid biopsy approach for the early diagnosis of NSCLC.

METHODS Exosomes were isolated from collected serum; their morphology was imaged using transmission electron microscopy (TEM); particle size was measured using a particle size analyzer; and the expression of exosomal membrane proteins was identified using Western blot. Gene chips were used to screen for differentially expressed snoRNAs in exosomes, which were further validated by quantitative PCR (qPCR). The area under the receiver operating characteristic (ROC) curve (AUC) was used to estimate their diagnostic performance for NSCLC. Their biological functions in NSCLC were evaluated using an in vitro study.

RESULTS A series of exosome characterization experiments confirmed successful exosome extraction. Microarray and qPCR analyses revealed that serum exosomal snoRNAs (AC092799.1-201 and AC009408.1-201) were significantly upregulated in individuals with NSCLC. When combined with CEA and CYFRA21-1, these two exosomal snoRNAs achieved diagnostic efficacy of 0.948 and early diagnostic efficacy of 0.917. Cell experiments confirmed that AC092799.1-201 is related to rapid proliferation and high invasiveness of tumor cells.

CONCLUSION Exosomal snoRNAs AC092799.1-201 and AC009408.1-201, merged with CEA and CYFRA21-1, can serve as a novel liquid biopsy approach for the early diagnosis of NSCLC.