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Peer-reviewedCC BY 4.0Frontiers in Oncology

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

  • Hasan Riza Aydin1
  • Ibrahim Sibal1
  • Orhan Semerci2
  • Hamit Zafer Aksoy1
  • Fevzi Bedir3
  • Volkan Enes Çelik1
  • Sema Misir4
  • Serap Ozer Yaman5
5 affiliations
  1. 1Department of Urology, Faculty of Medicine, Trabzon University, Trabzon Kanuni Training and Research Hospital
  2. 2Department of Pathology, Trabzon Kanuni Training and Research Hospital
  3. 3Department of Urology, Erzurum Faculty of Medicine, Health Sciences University, Erzurum City Hospital
  4. 4Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University
  5. 5Department of Medical Biochemistry, Faculty of Medicine, Trabzon University, Trabzon Kanuni Training and Research Hospital
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Cite

BibTeXRIS
BibTeX
@article{aydin2026stagespecific,
  title = {{Stage-specific miR-188-5p and ER stress markers reflect tumor aggressiveness in prostate cancer}},
  author = {Hasan Riza Aydin and Ibrahim Sibal and Orhan Semerci and Hamit Zafer Aksoy and Fevzi Bedir and Volkan Enes Çelik and Sema Misir and Serap Ozer Yaman},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1886215},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1886215/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Stage-specific miR-188-5p and ER stress markers reflect tumor aggressiveness in prostate cancer
AU  - Hasan Riza Aydin
AU  - Ibrahim Sibal
AU  - Orhan Semerci
AU  - Hamit Zafer Aksoy
AU  - Fevzi Bedir
AU  - Volkan Enes Çelik
AU  - Sema Misir
AU  - Serap Ozer Yaman
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1886215
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1886215/full
AB  - Background: 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.  Methods: 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.  Results: 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.  Conclusion: 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.
SN  - 2234-943X
ER  -