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Research

Predictive value of circulating microRNA-21 levels in patients with advanced non-small cell lung cancer treated with immunotherapy

16 Sep 2025
Cong Wang, Shan Jiang, Junfang Bi, Xu Xu

Background: Pembrolizumab has been widely used to curb the disease progression of non-small-cell lung cancer (NSCLC), but 20% of patients treated with pembrolizumab have disease progression. MicroRNA-21 (miRNA-21) was highly expressed in NSCLC and promoted the occurrence of malignancy-related processes. However, the predictive value of miR-21 in NSCLC patients who underwent immunotherapy remains unknown. We aim to investigate the predictive role of miR-21 in NSCLC patients who received pembrolizumab-based combination therapy.

Methods: We included 136 advanced NSCLC patients and miR-21 levels were identified. The combined positive score (CPS) was calculated and CPS≥1 was considered PD-L1 positive tumour cells in patients with NSCLC. Circulating miR-21 expressions between responders and non-responders were analysed. The overall survival (OS) and progression-free survival (PFS) according to miR-21 status were also investigated.

Results: Patients categorised as responders had significantly lower expression of miRNA-21 (p < 0.001). Notably, miR-21 levels were also lower in patients with CPS≥1 (p < 0.001). According to the 50th percentile of miR-21 concentrations, patients with lower miR-21 levels had significantly improved OS (69.6 (95% CI: 63.8–75.4) versus 14.4 (95% CI: 9.9–18.9), p<0.001) and PFS than those with higher miR-21 levels (64.2 (95% CI: 58–70.4) versus 17.0 (95% CI: 16.5–17.5), p<0.001).

Conclusion: MiR-21 levels were significantly correlated with the therapeutic effect and prognosis of NSCLC patients who received immunotherapy. MiR-21 holds promise as a potential biomarker of response to immunotherapy in NSCLC and it may suggest that miR-21 could be regarded as a novel indicator for prognostic prediction in NSCLC patients.

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