Lectin-captured plasma microRNAs predict response and survival in patients with non-small cell lung cancer treated...

Predictive biomarkers for response and post-treatment survival of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are limited. The present study aimed to evaluate whether recombinant Oscillatoria agardhii agglutinin (OAA)1-enriched plasma microRNAs (miRNAs/miRs) can serve as predictive and prognostic biomarkers in patients with NSCLC treated with nivolumab. High-mannose glycans, enriched in tumors, were selectively captured using this novel lectin. Pre-treatment plasma samples from 48 patients with NSCLC treated with nivolumab, an ICI, were processed using OAA1 columns. Plasma miRNAs were evaluated for their potential roles as predictive markers of response to nivolumab. The levels of circulating miR-320a, miR-320b and miR-3613-5p, which are associated with nivolumab resistance, were quantified with and without OAA1 enrichment. The three miRNAs were significantly upregulated in patients with stable or progressive disease compared with those with a partial response. For miR-320a, this difference was significant only after OAA1 enrichment. Receiver operating characteristic curve and survival analyses showed improved predictive and prognostic performance for OAA1-enriched miRNAs: The area under the curve for miR-3613-5p improved from 0.837 to 0.897, and the hazard ratio increased from 3.386 to 7.815. In conclusion, OAA1-enriched plasma miRNAs may be associated with resistance to nivolumab and a poor prognosis in NSCLC. This glycan-based enrichment strategy could enhance the clinical value of circulating miRNAs and may complement tissue-based biomarkers of ICI response.