PLA2G10 incorporated in exosomes could be diagnostic and prognostic biomarker for non-small cell lung cancer

Background: Exosomal cargos such as nucleic acids and proteins have been attracting major interest as promising diagnostic biomarkers of cancers. The aim of this study was to characterize the mRNA profiles of serum exosomes and to identify non-small cell lung cancer (NSCLC) related mRNAs with higher sensitivity and specificity to diagnose and predict prognosis of NSCLC.

Methods: mRNA microarray analysis was conducted to screen differentially expressed mRNAs in the serum exosomes of NSCLC patients. Selected exosomal mRNA candidate PLA2G10 and PLA2G10 protein were quantified by RT-qPCR and ELISA assay, respectively, in the sample cohorts of healthy, benign lung tumor and NSCLC. Receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic power of exosomal PLA2G10 mRNA and protein. Kaplan-Meier plots were used to estimate patients' overall and disease-free survival.

Results: Serum exosomal PLA2G10 mRNA levels were elevated in NSCLC patients, and were closely related to more aggressive characteristics (higher stages, lymphatic node metastasis and distant metastasis) and poor overall and disease-free survival of NSCLC patients. Intriguingly, PLA2G10 protein was proved to be incorporated in exosomes, and its expression patterns and relationship with clinical pathological factors were similar to exosomal PLA2G10 mRNA. Additionally, the levels of exosomal PLA2G10 mRNA and protein were positively correlated and their combination could improve the diagnostic power to discriminate less and more malignance of NSCLC.

Conclusions: Increased levels of serum exosomal PLA2G10 mRNA and protein were associated with more aggressive features of NSCLC, suggesting their potential as diagnostic and prognostic biomarkers of NSCLC.