Clinical Significance In Prostate Cancer Research Articles

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Somatic Tumor Testing in Prostate Cancer: Experience of a Tertiary Care Center Including Pathologist-Driven Reflex Testing of Localized Tumors at Diagnosis

Somatic tumor testing in prostate cancer (PCa) can guide treatment options by identifying clinically actionable variants in DNA damage repair (DDR) genes, including acquired variants not detected by germline testing alone. Guidelines currently recommend performing somatic tumor testing in metastatic PCa, while there is no consensus on the role of testing in regional disease and the optimal testing strategy is involving. This study evaluates the frequency, distribution, and pathologic correlates of somatic DDR mutations in metastatic and localized PCa following the implementation of pathologist-driven reflex testing at diagnosis. A cohort of 516 PCa were sequenced using a custom NGS panel including homologous recombination repair (HRR) and mismatch repair (MMR) genes. Variants were classified based on the AMP/ASCO/CAP guidelines. In total 183 (35.5%) patients had at least one variant: 72/516 (13.9%) had at least one Tier I or Tier II variant while 111/516 (21.5%) had a Tier III variant. Tier I/II variant(s) were identified in 27% (12/44) of metastatic biopsies and 13% (61/472) of primary samples. Overall, 12% (62/516) of patients had at least one Tier I/II variant in a HRR gene while 2.9% (10/516) had at least one Tier I/II variant in a MMR gene. The presence of a Tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal/cribriform carcinoma in the primary tumor. Among 309 reflex-tested hormone-naïve primary tumors, Tier I/II variants were identified in 10% (31/309) of cases: 9.2% (9/98) GG2; 9% (9/100) GG3; 9.1% (4/44) GG4 and 13.4% (9/67) GG5 cases. Our findings confirm the utility of somatic tumor testing to detect variants of clinical significance in PCa and provide insights that can inform the design of testing strategies. Pathologist-initiated reflex testing streamlines the availability of the results for clinical decision-making, however pathologic parameters such as grade group and intraductal/cribriform carcinoma may not be reliable to guide patient selection.

Clinical significance of prostate cancer identified by transperineal standard template biopsy in men with nonsuspicious multiparametric magnetic resonance imaging

ObjectiveMultiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csCaP). However, whether a negative mpMRI in patients with a clinical suspicion of CaP can omit a confirmatory biopsy remains less understood and without consensus. Transperineal (TP) standard template biopsy (SBx) provides an effective approach to CaP detection. Our aim is to provide a comprehensive understanding of the CaP characteristics detected through TP SBx that are systematically overlooked by mpMRI. MethodsWe conducted a retrospective analysis of all men who underwent prebiopsy mpMRI and subsequent a 20-core TP SBx at our hospital from September 2019 to February 2021. Patients with suspicious mpMRI received a combined TP SBx and targeted biopsy (TBx) (suspicious group), while those without suspicious (negative) mpMRI and who proceeded to biopsy, received TP SBx only (nonsuspicious group). A negative mpMRI was defined as the absence of suspicious findings and/or the presence of low-risk areas with a PI-RADS score of ≤2. Subsequently, we compared and evaluated the clinical and biopsy characteristics between these 2 groups. ResultsWe identified 301 men in suspicious group and 215 men in nonsuspicious group. The overall CaP detection rate and csCaP detection rate by TP SBx were 74.1%, 38.9% for suspicious group and 43.3%, 14.9% for nonsuspicious group, respectively. csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. The greatest percentage of cancer involvement (GPC) in biopsy core from nonsuspicious group was significantly lower than those of suspicious group (40% vs. 50%, p = 0.005), In multivariate logistic analysis, only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. ConclusionWithin our cohort, false-negative rates of mpMRI for csCaP are substantial, reaching 15%. Nonsuspicious cases may contain a large volume tumor since the high GPC of SBx. For cases with nonsuspicious imaging and higher PSAD, a confirmatory biopsy may be necessary due to the increased risk of missed csCaP by mpMRI.

High expression of centromere protein A and its molecular mechanism and clinical significance in prostate cancer: A study based on data mining and immunohistochemistry.

The progression of prostate cancer (PCa) leads to poor prognosis. However, the molecular mechanism of PCa is still not completely clear. This study aimed to elucidate the important role of centromere protein A (CENPA) in PCa. Large numbers of bulk RNA sequencing (RNA-seq) data and in-house immunohistochemistry data were used in analysing the expression level of CENPA in PCa and metastatic PCa (MPCa). Single-cell RNA-seq data was used to explore the expression status of CENPA in different prostate subpopulations. Enrichment analysis was employed to detect the function of CENPA in PCa. Clinicopathological parameters analysis was utilised in analysing the clinical value of CENPA. The results showed that CENPA was upregulated in PCa (standardised mean difference [SMD]=0.83, p=0.001) and MPCa (SMD=0.61, p=0.029). CENPA was overexpressed in prostate cancer stem cells (CSCs) with androgen receptor (AR) negative compared to epithelial cells with AR positive. CENPA may influence the development of PCa through affecting cell cycle. Patients with nodal metastasis had higher expression level of CENPA. And patients with high CENPA expression had poor disease-free survival. Taken together, Overexpression of CENPA may influence the development of PCa by regulating cell cycle and promoting metastasis.

GNL3 and PA2G4 as Prognostic Biomarkers in Prostate Cancer.

Prostate cancer is a multifocal and heterogeneous disease common in males and remains the fifth leading cause of cancer-related deaths worldwide. The prognosis of prostate cancer is variable and based on the degree of cancer and its stage at the time of diagnosis. Existing biomarkers for the prognosis of prostate cancer are unreliable and lacks specificity and sensitivity in guiding clinical decision. There is need to search for novel biomarkers having prognostic and predictive capabilities in guiding clinical outcomes. Using a bioinformatics approach, we predicted GNL3 and PA2G4 as biomarkers of prognostic significance in prostate cancer. A progressive increase in the expression of GNL3 and PA2G4 was observed during cancer progression having significant association with poor survival in prostate cancer patients. The Receiver Operating Characteristics of both genes showed improved area under the curve against sensitivity versus specificity in the pooled samples from three different GSE datasets. Overall, our analysis predicted GNL3 and PA2G4 as prognostic biomarkers of clinical significance in prostate cancer.

CRISPR screening reveals gleason score and castration resistance related oncodriver ring finger protein 19 A (RNF19A) in prostate cancer.

Prostate cancer (PCa) is one of the most lethal causes of cancer-related death in male. It is characterized by chromosomal instability and disturbed signaling transduction. E3 ubiquitin ligases are well-recognized as mediators leading to genomic alterations and malignant phenotypes. There is a lack of systematic study on novel oncodrivers with genomic and clinical significance in PCa. In this study we used clustered regularly interspaced short palindromic repeats (CRISPR) system to screen 656 E3 ubiquitin ligases as oncodrivers or tumor repressors in PCa cells. We identified 51 significantly changed genes, and conducted genomic and clinical analysis on these genes. It was found that the Ring Finger Protein 19A (RNF19A) was a novel oncodriver in PCa. RNF19A was frequently amplified and highly expressed in PCa and other cancer types. Clinically, higher RNF19A expression correlated with advanced Gleason Score and predicted castration resistance. Mechanistically, transcriptomics, quantitative and ubiquitination proteomic analysis showed that RNF19A ubiquitylated Thyroid Hormone Receptor Interactor 13 (TRIP13) and was transcriptionally activated by androgen receptor (AR) and Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A). This study uncovers the genomic and clinical significance of a oncodriver RNF19A in PCa. The results of this study indicate that targeting AR/HIF1A-RNF19A-TRIP13 signaling axis could be an alternative option for PCa diagnosis and therapy.

Prostate Cancer Detection with mpMRI According to PI-RADS v2 Compared with Systematic MRI/TRUS-Fusion Biopsy: A Prospective Study.

Background: mpMRI assesses prostate lesions through their PI-RADS score. The primary goal of this prospective study was to demonstrate the correlation of PI-RADS v2 score and the volume of a lesion with the presence and clinical significance of prostate cancer (PCa). The secondary goal was to determine the extent of additionally PCa in inconspicuous areas. Methods: All 157 patients underwent a perineal MRI/TRUS-fusion prostate biopsy. Targeted biopsies as well as a systematic biopsy were performed. The presence of PCa in the probes was specified by the ISUP grading system. Results: In total, 258 lesions were biopsied. Of the PI-RADS 3 lesions, 24% were neoplastic. This was also true for 36.9% of the PI-RADS 4 lesions and for 59.5% of the PI-RADS 5 lesions. Correlation between ISUP grades and lesion volume was significant (p < 0.01). In the non-suspicious mpMRI areas carcinoma was revealed in 19.7% of the patients. Conclusions: The study shows that the PI-RADS v2 score and the lesion volume correlate with the presence and clinical significance of PCa. However, there are two major points to consider: First, there is a high number of false positive findings. Second, inconspicuous mpMRI areas revealed PCa.

The expression and significance of p4E-BP1/4E-BP1 in prostate cancer.

BackgroundAlthough the phosphorylation of 4E‐BP1 that has been detected in high‐grade prostate cancer has been reported in previous studies, overexpression of p4E‐BP1 and 4EBP1 and their clinical significance in prostate cancer still remain unknown.MethodsOne hundred six samples of prostate tissues were collected and analyzed by immunohistochemistry with p4E‐BP1 or 4E‐BP1 specific antibodies. Everolimus was used to block the phosphorylation of p4E‐BP1, and then flow cytometry, clone formation, transwell, and wound healing assays were performed to detect the survival and invasive ability of the prostate cancer cells.ResultsWe found that the expression of 4E‐BP1 and p4E‐BP1 was higher in prostate cancer tissues than in normal tissues. Interestingly, the expression of p4E‐BP1 was significantly associated with Gleason score and lymph node metastasis, but had no obvious correlation with PSA and the presence of bone or visceral metastasis. However, no evident correlation was found between the positive expression of 4E‐BP1 and these clinical characteristics. In in vitro experiments, we found similar results as the clinical presentation that 4E‐BP1 and p4E‐BP1 were low expressed in normal prostate epithelial cells, but in prostate cancer cells, as the malignancy increasing, 4E‐BP1 and p4E‐BP1 expression also gradually increased. Then, we used Everolimus to inhibit the phosphorylation of 4E‐BP1 and found that Everolimus effectively reduced cloning formation, inhibited cell migration, and promoted apoptosis in a dose‐dependent manner in PC3 cells.ConclusionsThese findings suggest that p4E‐BP1 is a potential biomarker and therapy target for prostate cancer, and patients with high expressions of p4E‐BP1 may benefit from Everolimus treatment.

Comprehensive analysis of tumour mutational burden and its clinical significance in prostate cancer

BackgroundThe tumorigenesis of prostate cancer involves genetic mutations. Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immunotherapy.ResultsSingle-nucleotide polymorphisms were the most common variant type, and C>T transversion was the most commonly presented type of single-nucleotide variant. The high-TMB group had lower overall survival (OS) than the low-TMB group. TMB was associated with age, T stage and N stage. Functional enrichment analysis of differentially expressed genes (DEGs) showed that they are involved in pathways related to the terms spindle, chromosomal region, nuclear division, chromosome segregation, cell cycle, oocyte meiosis and other terms associated with DNA mutation and cell proliferation. Six hub genes, PLK1, KIF2C, MELK, EXO1, CEP55 and CDK1, were identified. All the genes were associated with disease-free survival, and CEP55 and CDK1 were associated with OS.ConclusionsThe present study provides a comprehensive analysis of the significance of TMB and DEGs and infiltrating immune cells related to TMB, which provides helpful information for exploring the significance of TMB in prostate cancer.

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

BackgroundExtracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance.MethodsSTEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSKCC, and SU2C/PCF Dream Team).ResultsEvaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified.ConclusionsSTEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.

Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Objective:Anoctamin 7 (ANO7) is a calcium2+-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence (P < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strong ANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- or postoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11 chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa.

Aberrant Expression of Citrate Synthase is Linked to Disease Progression and Clinical Outcome in Prostate Cancer.

PurposeCitrate synthase (CS) is a rate-limiting enzyme in the citrate cycle and is capable of catalyzing oxaloacetate and acetyl-CoA to citrate. CS has been uncovered to be upregulated in a variety of cancers, and its expression and clinical significance in prostate cancer (PCa) remain unknown.MethodsIn this study, we examined the association between CS expression level and clinicopathological features of prostate cancer patients in a TMA cohort and the public cancer database (The Cancer Genome Atlas-Prostate Adenocarcinoma, TCGA-PRAD). The CS knockdown cell lines were constructed to study the effects of CS downregulation on proliferation, colony formation, migration, invasion, and cell cycle of prostate cancer cells in vitro. And the effect of CS downregulation on tumor growth in mice was studied in vivo. In addition, the metabolomics and mitochondrial function were detected in the CS knockdown cell lines.ResultsCS expression level in PCa tissues was higher than that in normal tissues (P < 0.05). CS upregulation was significantly associated with high Gleason score (P < 0.05), advanced pathological stage (P < 0.001), and biochemical recurrence (P < 0.001). Functionally, decreased expression of CS inhibited PCa cell proliferation, colony formation, migration, invasion and cell cycle in vitro, and inhibited tumor growth in vivo. In addition, CS downregulation exerted potential inhibitory effects on the lipid metabolism and mitochondrial function of PCa cells.ConclusionIn conclusion, these findings suggested that CS upregulation may contribute to the aggressive progression and poor prognosis of PCa patients, which might be partially associated with its influences on the cell lipid metabolism and mitochondrial function.

Doublecortin Expression in Prostate Adenocarcinoma and Neuroendocrine Tumors

Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer. DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC) and compared across disease states, histologic grades, and clinical outcomes. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and overall survival (OS) were analyzed using Cox proportional hazards. DCX expression was not significantly different among normal prostate (n = 29), primary prostate cancer (n=131), and metastases (n = 19) and did not increase with grade in a large cohort of radical prostatectomy samples (n = 17,967). Those with DCX expression above and below the median did not have significant differences in BRFS (HR 1.15 [95% confidence interval, 0.88-1.49], P = .31), MFS (HR 1.2 [0.84-1.7], P = .3), or OS (HR 1.15 [0.7-1.84], P = .56). In a cohort with untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n = 10) compared with grade group 5 prostate adenocarcinoma (n = 110) (P = .007). Similarly, in 2 cohorts with mCRPC (n = 290), DCX expression was higher in lesions with neuroendocrine features compared with adenocarcinoma (P < .001). Contrary to recent data using mouse models, DCX expression did not differ by disease state or outcome and did not increase with grade in a large data set of patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine histology, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX and its clinical significance in prostate cancer.

Novel Long Non-coding RNA lncAMPC Promotes Metastasis and Immunosuppression in Prostate Cancer by Stimulating LIF/LIFR Expression

Long non-coding RNAs (lncRNAs) participate in the development and progression of prostate cancer (PCa). We aimd to identify a novel lncRNA, named lncRNA activated in metastatic PCa (lncAMPC), and investigate its mechanisms and clinical significance in PCa. First, the biological capacity of lncAMPC in PCa was demonstrated both invitro and invivo. The lncAMPC was overexpressed in tumor tissue and urine of metastatic PCa patients and promoted PCa tumorigenesis and metastasis. Then, a mechanism study was conducted to determine how the lncAMPC-activated pathway contributed to PCa metastasis and immunosuppression. In the cytoplasm, lncAMPC upregulated LIF expression by sponging miR-637 and inhibiting its activity. In the nucleus, lncAMPC enhanced LIFR transcription by decoying histone H1.2 away from the upstream sequence of the LIFR gene. The lncAMPC-activated LIF/LIFR expressions stimulated the Jak1-STAT3 pathway to simultaneously maintain programmed death-ligand 1 (PD-L1) protein stability and promote metastasis-associated gene expression. Finally, the prognostic value of the expression of lncAMPC and its downstream genes in PCa patients was evaluated. High LIF/LIFR levels indicated shorter biochemical recurrence-free survival among patients who underwent radical prostatectomy. Therefore, the lncAMPC/LIF/LIFR axis plays a critical role in PCa metastasis and immunosuppression and may serve as a prognostic biomarker and potential therapeutic target.

Applied anatomy of pelvic lymph nodes and its clinical significance for prostate cancer:a single-center cadaveric study

BackgroundPelvic lymph node dissection (PLND) is one of the most important steps in radical prostatectomy (RP). Not only can PLND provide accurate clinical staging to guide treatment after prostatectomy but PLND can also improve the prognosis of patients by eradicating micro-metastases. However, reports of the number of pelvic lymph nodes have generally come from incomplete dissection during surgery, there is no anatomic study that assesses the number and variability of lymph nodes. Our objective is to assess the utility of adopting the lymph node count as a metric of surgical quality for the extent of lymph node dissection during RP for prostate cancer by conducting a dissection study of pelvic lymph nodes in adult male cadavers.MethodsAll 30 adult male cadavers underwent pelvic lymph node dissection (PLND), and the lymph nodes in each of the 9 dissection zones were enumerated and analyzed.ResultsA total of 1267 lymph nodes were obtained. The number of lymph nodes obtained by limited PLND was 4–22 (14.1 ± 4.5), the number obtained by standard PLND was 16–35 (25.9 ± 5.6), the number obtained by extended PLND was 17–44 (30.0 ± 7.0), and the number obtained by super-extended PLDN was 24–60 (42.2 ± 9.7).ConclusionsThere are substantial inter-individual differences in the number of lymph nodes in the pelvic cavity. These results have demonstrated the rationality and feasibility of adopting lymph node count as a surrogate for evaluating the utility of PLND in radical prostatectomy, but these results need to be further explored.

Expression of anoctamin 7 in nuclear factor kappa B signal pathway and its clinical significance in prostate cancer

Objective To study the Expression of anoctamin 7 (ANO7) in the nuclear factor kappa B (NF-κB) signal pathway and its clinical significance in prostate cancer. Methods NF-κB signal pathway activated cell and animal model were constructed using tribbles homolog1 (TRIB1) overexpressed prostate cancer cell line. NF-κB signal pathway inhibited cell model was constructed using NF-κB signal pathway inhibitor. Western blotting and real-time quantitative polymerase chain reaction (Real-time PCR) and immunohistochemistry (IHC) were used to analyze the effect of NF-κB signal pathway on the regulation of ANO7 expression and the relationship between ANO7 expression and clinicopathological features in prostate cancer. Results ANO7 expression was up-regulated in the NF-κB signal pathway-activated cell and animal models. ANO7 expression was down-regulated in the NF-κB signal pathway-inhibited cell models. The high expression level of ANO7 was 45.8% in tumor tissues compared with 85.7% in adjacent non-cancerous tissues, with statistical significance (χ2=7.258, P<0.01). The expression of ANO7 was significantly correlated with Gleason score and pathological grade (χ2=19.797, 19.797, P<0.01). Similar results were obtained from The Cancer Genome Atlas (TCGA) and the Taylor database. Kaplan-Meier analysis found that ANO7 was significantly associated with the patients’prognosis in the Taylor database (P<0.01). Multivariate analysis found that ANO7 (P<0.05), Gleason score (P<0.01) and pathological grade (P<0.01) were independent predictors of prostate cancer using the Cox regression model in the cohort affecting prostate cancer prognosis. Conclusion NF-κB signal pathway regulates ANO7 expression in prostate cancer and the expression of ANO7 is closely related to prostate cancer. Key words: Anoctamin 7; Nuclear factor kappa B signal pathway; Prostate cancer; Prognosis

Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer

Altered glutamine metabolism is a hallmark of cancer growth, forming the theoretical basis for development of metabolic therapies as cancer treatments. Glutaminase (GLS), a crucial enzyme involved in the regulation of glutamine metabolism, has been reported to play crucial roles in cancer development. However, the precise function of GLS in prostate cancer (PCa) remains unclear. The purpose of the present study was to assess the GLS expression and its clinical significance in PCa. We found that GLS was significantly up-regulated in PCa tissues and cell lines. High expression of GLS was significantly associated with Gleason score (P=0.001) and Tumor stage (P=0.015). Functionally, we silenced GLS in PCa cell lines and revealed that GLS knockdown largely blunted the proliferation of DU145 and PC-3 cells. Mechanistically, we demonstrated that knockdown of GLS induced apoptosis and cell cycle arrest. Moreover, we observed that the expressions of Bax were increased while the levels of cyclinD1 and Bcl-2 were decreased after knockdown of GLS in PCa cells. Importantly, through Western blot analysis, we identified that GLS knockdown dramatically suppressed Wnt/β-catenin pathway. Taken together, GLS is a novel oncogene in PCa and may be a potential treatment target for PCa patients.

Elevated expression of PTCD3 correlates with tumor progression and predicts poor prognosis in patients with prostate cancer.

Pentatricopeptide repeat domain protein 3 (PTCD3) is a mitochondrial RNA-binding protein that serves a role in mitochondrial translation. PTCD3 was originally reported as an oncogene that is involved in breast cancer and lymphoma. However, the expression and function of PTCD3 in prostate cancer (PCa) are unknown. Therefore, the aim of the present study was to investigate the expression of PTCD3 and its clinical significance in PCa. Immunohistochemistry and dataset analyses revealed that PTCD3 protein expression levels were enhanced in human PCa tissues and mouse PCa models. PTCD3 expression levels were positively correlated with advanced PCa pathological grade and clinical stage. Additionally, PTCD3 mRNA expression was positively correlated with tissue malignancy, high Gleason score and distant metastasis in The Cancer Genome Atlas dataset. Kaplan-Meier analysis revealed that high PTCD3 levels can predict the increased biochemical recurrence (BCR)-free survival in all patients with or without metastasis. The overexpression of PTCD3 could be used as an independent prognostic marker of poor BCR-free survival. Immunofluorescence and western blot analysis in human PCa cell lines further confirmed that PTCD3 levels were associated with the hormone independence of PCa. Therefore, the present study revealed that PTCD3 levels may serve as a novel biomarker for PCa prognosis.

Increased KIF4A expression is a potential prognostic factor in prostate cancer.

The kinesin super-family protein (KIF) 4A gene is reported to be overexpressed and associated with poor clinical prognosis in human cancers; however, its clinical significance in prostate cancer (PCa) has not been well studied. The present study performed dataset analyses and revealed that KIF4A expression was significantly increased in castration-resistant PCa patients. Additionally, KIF4A expression was significantly highly expressed in PCa tissues compared with non-cancerous tissues, particularly in advanced PCa pathological stages. Upregulated KIF4A mRNA expression in PCa tissues was significantly correlated with shorter overall survival and prostate-specific antigen failure. Furthermore, both univariate and multivariate analyses revealed that upregulated KIF4A may predict poor biochemical recurrence (BCR)-free survival. The data suggested that KIF4A may play a key role in PCa progression. Notably, increased KIF4A expression may potentially predict poor BCR-free survival in PCa patients.

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.