Urinary miR-574-5p as a candidate biomarker for early-stage lung adenocarcinoma: an exploratory case-control study

Background: Early detection of lung adenocarcinoma remains challenging despite advances in low-dose computed tomography (LDCT) screening. Urinary microRNAs (miRNAs) represent a non-invasive biomarker modality, but their clinical utility in early-stage disease remains unclear. This study aimed to identify urinary miRNA candidates associated with early-stage lung adenocarcinoma and to explore whether urinary miR-574-5p may provide complementary diagnostic information beyond established clinical risk factors.

Methods: We conducted an exploratory case-control study using urinary samples from the J-CAN cohort, a prospective biomarker study. Small RNA sequencing was performed to profile miRNAs. Candidate miRNAs were identified using edgeR and the Wilcoxon rank-sum test. Associations with lung cancer status were evaluated using multivariable Firth logistic regression adjusted for age, sex, smoking status, and urinary creatinine. Model performance was assessed using the area under the curve (AUC), and internal validation was performed using bootstrap resampling.

Results: A total of 77 participants (33 early-stage lung adenocarcinoma (stage 0–IA2) and 44 healthy controls) were included in the primary analysis. Among candidate miRNAs, miR-574-5p showed the most consistent overall signal. Urinary miR-574-5p expression was significantly decreased in patients with early-stage adenocarcinoma and remained independently associated with lung cancer status after adjustment [odds ratio (OR) 0.15, 95% confidence interval (CI): 0.02–0.53, P<0.001]. The baseline clinical model yielded an AUC of 0.961, which increased to 0.988 with the addition of miR-574-5p (ΔAUC =0.027), although this increase was not statistically significant.

Conclusions: Urinary miR-574-5p was decreased in early-stage lung adenocarcinoma and was independently associated with disease status. Although its incremental diagnostic value was modest, urinary miR-574-5p may provide limited complementary information beyond established clinical risk factors. Further validation in independent and prospective cohorts is warranted.