Serum GAS5, miR-320 and autophagy-related genes Beclin-1 and LC3 in coronary in-stent restenosis: Expression patterns and clinical correlations

Objective This study evaluated whether circulating GAS5, miR-320, Beclin-1, and LC3 are associated with angiographically confirmed in-stent restenosis (ISR) and its angiographic severity in patients after drug-eluting stent (DES) implantation. Methods In this retrospective matched observational study, 132 patients (60 ISR, 72 non-ISR) were stratified by coronary angiography within six months of PCI; 1:1 propensity score matching yielded 52 pairs (104 patients). Serum GAS5 and miR-320 (qRT-PCR) and Beclin-1 and LC3 (ELISA) were measured at baseline and at the six-month follow-up. Correlation, ROC, and regression analyses evaluated contemporaneous diagnostic accuracy and associations with ISR. Results After PSM, all SMDs were ≤ 0.27 (13 of 20 covariates < 0.10). ISR patients had higher GAS5, Beclin-1, and LC3 and lower miR-320 than non-ISR patients at both timepoints (all P < 0.001). All four biomarkers correlated with stenosis severity at both timepoints (Spearman |rs| = 0.25–0.60). Using six-month values obtained concurrently with angiography, the combined panel achieved an AUC of 0.88 (95% CI: 0.80–0.93), exceeding Beclin-1 and LC3 (both P < 0.01) and miR-320 (P = 0.041), with a non-significant trend versus GAS5 (P = 0.082). Lower miR-320 and higher Beclin-1 remained independently associated with ISR; conditional logistic regression confirmed miR-320 as the most robust marker (OR = 0.20 per SD, P = 0.023). Baseline (pre-PCI) analyses are reported separately as exploratory. Conclusion Serum GAS5, miR-320, Beclin-1, and LC3 are promising autophagy-related biomarkers for the contemporaneous discrimination of angiographically confirmed ISR, and combined detection improves diagnostic reliability. Because biomarkers and ISR were assessed at the same visit without longitudinal outcomes, these findings do not establish prospective prediction and require external validation.