Stage-specific miR-188-5p and ER stress markers reflect tumor aggressiveness in prostate cancer

Reliable biomarkers are required to improve the detection and risk stratification of prostate cancer (PCa), particularly for identifying aggressive disease. MicroRNAs (miRNAs) have emerged as promising candidates; however, their integration with endoplasmic reticulum (ER) stress pathways and their clinical relevance remain incompletely defined.

This study included 38 patients with histologically confirmed PCa and 20 individuals with benign biopsy findings. Patients were stratified into low-intermediate and high-risk groups based on clinical stage, Gleason score, and PSA levels. Expression levels of miR-188-5p, GRP78, and CHOP were quantified in prostate biopsy specimens using quantitative real-time PCR, and ELISA measured serum GRP78 and CHOP levels. In parallel, bioinformatic analyses were performed to predict candidate miR-188-5p interactions and to examine ER stress-related expression patterns using publicly available resources, including miRWalk, Sfold/STarMir, and GEPIA3 (TCGA/GTEx datasets). Associations between molecular markers and clinicopathological parameters were evaluated, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and exploratory univariate logistic regression.

Bioinformatic analyses identified HSPA5 (GRP78) and DDIT3 (CHOP) as candidate miR-188-5p targets with predicted binding sites. External dataset analysis demonstrated higher HSPA5 and lower DDIT3 expression in prostate adenocarcinoma than in normal tissues. These computational findings indicate predicted interactions and do not establish direct binding or regulation. Clinically, miR-188-5p and GRP78 expression levels were significantly elevated in PCa patients compared with controls and increased progressively with tumor aggressiveness (p<0.001), whereas CHOP expression decreased (p<0.001). miR-188-5p was positively correlated with GRP78 and inversely correlated with CHOP. Among the evaluated markers, miR-188-5p showed the highest diagnostic discrimination in this cohort, and the exploratory composite biomarker model achieved an AUC of 0.966. Elevated miR-188-5p and GRP78 levels were also associated with adverse pathological features, including higher tumor grade and cribriform pattern; however, these findings require independent validation.

Stage-associated alterations in miR-188-5p and the ER stress markers GRP78 and CHOP were associated with prostate cancer aggressiveness. The integrated computational and clinical findings support a potential expression-level relationship that may inform future biomarker studies, but they do not demonstrate direct miRNA-target binding or causal regulation.