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

**Authors:** Cong Wang, Shan Jiang, Junfang Bi, Xu Xu

PMC · DOI: 10.3332/ecancer.2025.1989 · ecancermedicalscience · 2025-09-16

## TL;DR

This study found that lower levels of microRNA-21 in the blood of lung cancer patients predicted better response and survival when treated with immunotherapy.

## Contribution

The study reveals miR-21 as a novel biomarker for predicting immunotherapy response and prognosis in non-small cell lung cancer.

## Key findings

- Lower miR-21 levels correlated with better treatment response in NSCLC patients receiving immunotherapy.
- Patients with lower miR-21 levels had significantly improved overall and progression-free survival.
- miR-21 levels were lower in patients with PD-L1 positive tumors.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Diseases:** non-small-cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}
- **Diseases:** NSCLC (MESH:D002289), malignancy (MESH:D009369)
- **Chemicals:** Pembrolizumab (MESH:C582435)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12812837/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12812837/full.md

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Source: https://tomesphere.com/paper/PMC12812837