Association Between Statin Exposure and Incidence and Prognosis of Prostate Cancer: A Meta-analysis Based on Observational Studies.

It is widely thought that statins have huge therapeutic potential against prostate cancer (PCA). This study aimed to investigate the effect of statin exposure on PCA incidence and prognosis. PubMed, Web of Science, Embase, and Cochrane databases were searched for observational studies on the association between statin exposure and PCA from inception until July 2022. The primary endpoints were the incidence of PCA and the survival rate. A total of 21 studies were included in this meta-analysis. The pooled estimates showed that exposure to hydrophilic statins was not associated with the incidence of PCA (odds ratio [OR]=0.94, 95% CI=0.88-1.01, P =0.075), while the incidence of PCA was significantly decreased in populations exposed to lipophilic statins compared with the nonexposed group (OR=0.94, 95% CI=0.90-0.98, P =0.001), mainly in Western countries (OR=0.94, 95% CI=0.91-0.98, P =0.006). Subgroup analysis showed that simvastatin (OR=0.83, 95% CI=0.71-0.97, P =0.016) effectively reduced the incidence of PCA. The prognosis of PCA in patients exposed to both hydrophilic (hazard ratio [HR]=0.57, 95% CI=0.49-0.66, P <0.001) and lipophilic (HR=0.65, 95% CI=0.58-0.73, P <0.001) statins were better than in the nonexposed group, and this improvement was more significant in the East than in Western countries. This study demonstrates that statins can reduce the incidence of PCA and improve prognosis, and are affected by population region and statin properties (hydrophilic and lipophilic).

Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

BACKGROUND: Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. METHODS: According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. RESULTS: A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1), while CDKN2A expression was significantly associated with a poor disease-free survival (P < .01). CONCLUSION: CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.

[Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways].

OBJECTIVE: To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such effects. METHODS: Human. ovarian cancer cells HO-8910PM were treated with evodiamine at 0, 1.25, 2.5, and 5 µM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910PM cells. The cell cycle was observed via propidium iodide (PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase (MAPK) and/or phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway-related proteins were also investigated. RESULTS: Evodiamine significantly inhibited the proliferation of HO-8910PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2 (Bcl-2) and an increase of Bcl-2-associated X protein (Bax) level. In addition, evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly (ADP-ribose)-polymerase (PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the activity of p38 MAPK. CONCLUSION: Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.