Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia.

OBJECTIVE: Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients. METHODS: The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification. RESULTS: The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers. CONCLUSIONS: This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

Association of gene polymorphisms of KLK3 and prostate cancer: A meta-analysis.

Previous studies have suggested that prostate-specific antigen (PSA) plays a role in the etiology of prostate cancer (PCa), and that polymorphisms of KLK3 may be associated with PCa. However, these results were conflicting. Therefore, we performed a meta-analysis to illuminate this problem. We searched the PubMed and Web of Science databases. Ten single nucleotide polymorphisms (SNPs) were involved in this meta-analysis. The pooled results showed that the minor alleles of rs1058205, rs2735839, rs174776, rs17632542, rs266849, rs266878, and rs2569735 were significantly associated with PCa. Compared to genotypes of the common homozygotes, the heterozygous genotypes of rs1058205, rs2735839, rs174776, rs17632542, rs266849, and rs266878 were significantly associated with PCa, as well as the homozygous genotypes of rs1058205, rs2735839, rs17632542, rs266878, rs266876, and rs2569735. Only rs2735839 was involved in the Gleason score (GS). The pooled results showed that when compared with GS ≥ 8 PCa, the A-allele was the protective factor for GS < 7 PCa. It was also a protective factor for GS ≥ 4+3 when compared to GS ≤ 3+4 PCa. A strong association was observed between PCa and rs1058205, rs2735839, rs266882, rs174776, rs17632542, rs266849, rs266878, rs266876, rs1058274, and rs2569735. The G-allele of rs2735839 was a risk factor for GS < 7 PCa when compared with the GS ≥ 8 PCa, as well as for the GS ≥ 4+3 when compared to the GS ≤ 3+4 PCa. Therefore, these SNPs may be valuable as biomarkers for PCa in the future.

Polymorphisms of vitamin D receptor gene TaqI susceptibility of prostate cancer: a meta-analysis.

OBJECTIVE: Many studies have investigated the association of the vitamin D receptor gene TaqI polymorphism with prostate cancer (PCa) risk. However, the evidence is inadequate to draw robust conclusions. To shed light on these inconclusive findings, we conducted a meta-analysis. MATERIALS AND METHODS: We searched PubMed for eligible articles. The relevant data were abstracted by two independent reviewers with the Stata 11.0 software. RESULTS: A total of 27 studies were included. The pooled outcomes indicated that the TaqI genetic polymorphisms were significantly associated with the risk of PCa (T vs t allele: odds ratio [OR] =1.11, 95% confidence interval [CI] =1.03-1.21, P=0.008; TT vs tt: OR =1.19, 95% CI =1.01-1.42, P=0.040; TT + Tt vs tt: OR =1.18, 95% CI =1.02-1.38, P=0.031), especially in the Asian population (T vs t allele: OR =1.11, 95% CI =1.03-1.21, P=0.008; TT/Tt vs tt: OR =1.93, 95% CI =1.02-3.66, P=0.043). In the tumor stage stratified analyses, the pooled results showed no significant difference in genetic polymorphisms between the local tumor group and the control group or between the local tumor group and the advanced tumor group. However, the genotypes TT and TT/Tt were significantly higher in the advanced PCa group compared to the control group (T vs t allele: OR =1.20, 95% CI =1.01-1.42, P=0.040; TT vs tt: OR =1.34, 95% CI =1.08-1.67, P=0.009; TT/Tt vs tt: OR =1.28, 95% CI =1.05-1.56, P=0.015). CONCLUSION: The vitamin D receptor gene TaqI allele polymorphism might be associated with a PCa risk, especially in Asians, which might provide new clues for the pathogenesis research and clinical diagnosis of PCa in the future.

Correlation between XRCC1 Arg399Gln genetic polymorphisms and susceptibility to bladder cancer: a meta-analysis.

The relationship between XRCC1 polymorphisms and bladder cancer has been widely studied. Here, our meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in XRCC1 and susceptibility to bladder cancer. In order to derive a more precise estimation of the association, 27 clinical case-control studies (which met all the inclusion criteria) were included in this meta-analysis. A total of 8,539 cancer cases and 10,750 controls were involved in this meta-analysis. Overall, no significant association was detected in allelic model (A allele vs T allele odds ratio [OR] =0.87, 95% confidence interval [CI], 0.71-1.06), homozygote comparison (AA vs GG OR =1.12, 95% CI, 0.68-1.85), heterozygote comparison (AT vs TT OR =1.01, 95% CI, 0.81-1.26), dominant model (AA + AG vs GG OR =0.93, 95% CI, 0.85-1.02), and recessive model (AA vs AG + GG OR =1.01, 95% CI, 0.88-1.15), but a moderately significant association was found for AG vs GG (OR =0.241, 95% CI =0.17-0.35). Subgroup analysis based on ethnicity. Ethnicity analysis suggested that genetic polymorphisms in XRCC1 were not correlated with increased bladder cancer risk among Asians (all P>0.05). Therefore, we concluded that XRCC1 genetic polymorphism may not contribute to bladder cancer susceptibility in the present meta-analysis, and further well-designed studies with a large sample size are warranted to validate our conclusion.

The association of tea consumption and the risk and progression of prostate cancer: a meta-analysis.

Many studies have focused on the association of tea consumption and the risk and progression of prostate cancer (PCa). However, the evidence is inadequate to draw robust conclusions. To shed light on these inconclusive findings, we conducted a meta-analysis. We searched the database of PubMed and Web of Science for eligible articles. The relevant data were abstracted by two independent reviewers and performed with Stata 11.0. 21 studies were included. The pooled outcomes showed that there was a significant association between tea consumption and PCa risk (OR=0.84, 95% CI (0.71-0.98)); tea consumption could reduce PCa risk in China and India (OR=0.40 and 0.48, 95% CI (0.25-0.66) and (0.24-0.97), respectively); both green and black tea consumption showed no significant effect on PCa risk (OR=0.73 and 0.95, 95% CI (0.52-1.02) and (0.82-1.11), respectively); the highest level tea consumption showed significant protective effect on the low-grade PCa (OR=0.66, 95% CI (0.46-0.93)); no significant effect was found in both localized and advanced PCa in stage subgroup analyses (OR=1.12 and 0.85, 95% CI (0.82-1.54) and (0.62-1.16), respectively). The results show that regardless of tea type, tea consumption might be a potential protective factor for the PCa, especially in China and India. Tea consumption might be the protective factor for low-grade PCa. However, more relevant studies are needed to further explore this association.