# Voiding symptoms aggravate with decreasing stromal/epithelial ratio and increasing glandular-epithelial content in patients undergoing laser enucleation for benign prostatic hyperplasia, independently from prostate size

**Authors:** Patrick Keller, Sheng Hu, Wenbin Zhu, Yajie Xu, Laurenz Berger, Philip Nicola, Philipp Weinhold, Alexander Tamalunas, Christian G. Stief, Martin Hennenberg

PMC · DOI: 10.1371/journal.pone.0345306 · PLOS One · 2026-03-24

## TL;DR

This study finds that worsening voiding symptoms in men with enlarged prostates are linked to higher levels of glandular cells, not stromal tissue, which may explain why some patients don't respond to certain drugs.

## Contribution

The study identifies glandular-epithelial content as a key driver of voiding symptoms in BPH, independent of prostate size or stromal factors.

## Key findings

- Voiding symptoms worsen with higher keratin-19 (glandular epithelial) expression.
- Prostate volume correlates negatively with calponin-1 (smooth muscle) mRNA expression.
- Stromal/epithelial ratio positively correlates with urinary flow rate.

## Abstract

Benign prostatic hyperplasia (BPH) includes epithelial, stromal and mixed hyperplasia, but their specific contributions to voiding symptoms and prostate volume (PV) are unknown. Here, we examined relationships of symptoms and PV with stromal and epithelial markers in patients undergoing laser enucleation for BPH.

Tissues were obtained from holmium or thulium laser enucleation of the prostate (n = 146 patients). Expressions of the smooth muscle marker calponin-1 (CNN1) and the glandular-epithelial cell marker keratin-19 (KRT19) were assessed by RT-PCR and Western blot, and analyzed for correlation with international prostate symptom score (IPSS), maximum urinary flow rate (Qmax), and PV.

The ratio of CNN1/KRT19 mRNA correlated positively with Qmax (r = 0.3809, p = 0.0263), and by trend negatively with IPSS (r = −0.2161, p = 0.0944). Accordingly, the IPSS increased with keratin protein expression (r = 0.4244, p = 0.0307), while the Qmax tended to correlate negatively with keratin expression (r = −0.2058, p = 0.4999). PV correlated negatively with CNN1 mRNA expression (r = −0.205, p = 0.0405). The inverse correlation of CNN1 with PV persisted in patients without catheterization (r = −0.2568, p = 0.0457), but was lacking in catheterized patients after separated analyses.

Voiding symptoms in patients undergoing laser enucleation for BPH aggravate with increasing keratin content. Symptoms in patients needing surgery for BPH depend rather on glandular-epithelial hyperplasia, but not on stromal hyperplasia, what might explain why these patients are refractory to treatment with α1-blockers.

## Linked entities

- **Genes:** CNN1 (calponin 1) [NCBI Gene 1264], KRT19 (keratin 19) [NCBI Gene 3880]
- **Proteins:** CNN1 (calponin 1), KRT24 (keratin 24)
- **Diseases:** benign prostatic hyperplasia (MONDO:0010811), BPH (MONDO:0010811)

## Full-text entities

- **Genes:** POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, CNN1 (calponin 1) [NCBI Gene 1264] {aka HEL-S-14, SMCC, Sm-Calp}, KRT18 (keratin 18) [NCBI Gene 3875] {aka CK-18, CYK18, K18}
- **Diseases:** prostate cancer (MESH:D011471), bladder stones or diverticula (MESH:D001744), cancer (MESH:D009369), hematuria (MESH:D006417), urinary tract infections (MESH:D014552), urinary retention (MESH:D016055), glandular hyperplasia (MESH:D006965), renal insufficiency (MESH:D051437), PV (MESH:D011472), epithelial hyperplasia (MESH:D017573), BPH (MESH:D011470), overflow incontinence (MESH:D014549), urethral obstruction (MESH:D014524)
- **Chemicals:** SYBR Green I (MESH:C098022), holmium (MESH:D006695), Alpha1-blockers (-), polyacrylamide (MESH:C016679), nitrogen (MESH:D009584), benzamidine (MESH:C032157), SDS (MESH:D012967), HCl (MESH:D006851), tadalafil (MESH:D000068581), thulium (MESH:D013932), Tween 20 (MESH:D011136)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC13012515/full.md

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Source: https://tomesphere.com/paper/PMC13012515