Chemoradiotherapy Lowers Circulating miR-21 Levels in Stage III Lung Cancer Patients

Patients with stage III non-small cell lung cancer (NSCLC) who received definitive chemoradiotherapy (CRT) showed a marked drop in circulating levels of the microRNA miR-21, according to a prospective pilot study published in BMC Cancer. Blood samples were drawn before CRT began and again after the final radiation fraction, allowing each patient to serve as their own comparison.

The molecular measurements relied on quantitative real-time polymerase chain reaction (qRT-PCR), with expression values normalized to miR-16 and fold changes calculated using the standard 2^−ΔΔCt method. Median miR-21 expression fell from 2.365 before treatment to −2.060 afterward on the −ΔCt scale. The Hodges–Lehmann estimate of the paired difference was −4.783, with a 95% confidence interval spanning −6.430 to −2.920 and a p value below 0.001. In contrast, miR-155, which could be measured in 20 of the 21 patients, declined numerically from 2.895 to −0.373 but did not reach statistical significance (Hodges–Lehmann estimate, −1.219; 95% CI, −3.377 to 1.167; p = 0.294).

Beyond tracking the microRNAs themselves, the study explored whether their levels related to acute treatment toxicity and to thoracic dosimetric parameters—the radiation dose metrics used to plan lung cancer radiotherapy. Adverse events were graded with the Common Terminology Criteria for Adverse Events, version 5.0, during treatment and at one and three months afterward. Three patients developed grade 3 radiation esophagitis and two developed grade 3 radiation pneumonitis. Because these event numbers were so small, the investigators treated all toxicity subgroup findings as descriptive rather than definitive.

The most suggestive dosimetric finding involved miR-155. Post-treatment miR-155 expression showed nominal positive correlations with lung V5, the volume of lung receiving at least 5 gray (Spearman’s ρ = 0.493; 95% CI, 0.110–0.753; p = 0.023), and lung V20, the volume receiving at least 20 gray (ρ = 0.578; 95% CI, 0.166–0.817; p = 0.006), each analyzed in 21 patients. However, neither association survived correction for multiple comparisons, with false-discovery-rate-adjusted q values of 0.347 and 0.182, respectively. The authors accordingly concluded that these nominal links should not be regarded as established.

The trial was registered on ClinicalTrials.gov as NCT06015815, retrospectively registered on August 29, 2023, and the article was published open access on October 23, 2026. The study measured molecular changes and associations; it did not evaluate whether microRNA levels could predict or modify treatment outcomes.

Subject of Research: Changes in serum extracellular vesicle–enriched miR-21 and miR-155 during chemoradiotherapy for stage III NSCLC and their associations with acute toxicity and lung dose parameters

Article Title: Serum extracellular vesicle–enriched miR-21 and miR-155 and acute toxicity during chemoradiotherapy for stage III NSCLC: a prospective pilot study

Article References: Gumustepe, E., Kaplan, İ., Karabulut, H. G., Birgi, S. D., & Akyurek, S. (2026). Serum extracellular vesicle–enriched miR-21 and miR-155 and acute toxicity during chemoradiotherapy for stage III NSCLC: a prospective pilot study. BMC Cancer. https://doi.org/10.1186/s12885-026-16803-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16803-8

Keywords: miR-21, miR-155, extracellular vesicles, chemoradiotherapy, stage III NSCLC, radiation esophagitis, radiation pneumonitis, lung V5, lung V20, pilot study, qRT-PCR, biomarker