Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.

The pathogenesis of renal calcium-oxalate (CaOx) stones is complex and influenced by various metabolic factors. In parallel, palmitic acid (PA) has been identified as an upregulated lipid metabolite in the urine and serum of patients with renal CaOx stones via untargeted metabolomics. Thus, this study aimed to mechanistically assess whether PA is involved in stone formation. Lipidomics analysis of PA-treated renal tubular epithelial cells compared with the control samples revealed that α-linoleic acid and α-linolenic acid were desaturated and elongated, resulting in the formation of downstream polyunsaturated fatty acids (PUFAs). In correlation, the levels of fatty acid desaturase 1 and 2 (FADS1 and FADS2) and peroxisome proliferator-activated receptor α (PPARα) in these cells treated with PA were increased relative to the control levels, suggesting that PA-induced upregulation of PPARα, which in turn upregulated these two enzymes, forming the observed PUFAs. Lipid peroxidation occurred in these downstream PUFAs under oxidative stress and Fenton Reaction. Furthermore, transcriptomics analysis revealed significant changes in the expression levels of ferroptosis-related genes in PA-treated renal tubular epithelial cells, induced by PUFA peroxides. In addition, phosphatidyl ethanolamine binding protein 1 (PEBP1) formed a complex with 15-lipoxygenase (15-LO) to exacerbate PUFA peroxidation under protein kinase C ζ (PKC ζ) phosphorylation, and PKC ζ was activated by phosphatidic acid derived from PA. In conclusion, this study found that the formation of renal CaOx stones is promoted by ferroptosis of renal tubular epithelial cells resulting from PA-induced dysregulation of PUFA and phosphatidic acid metabolism, and PA can promote the renal adhesion and deposition of CaOx crystals by injuring renal tubular epithelial cells, consequently upregulating adhesion molecules. Accordingly, this study provides a new theoretical basis for understanding the correlation between fatty acid metabolism and the formation of renal CaOx stones, offering potential targets for clinical applications.

YAP is required for prostate development, regeneration, and prostate stem cell function.

Prostate development and regeneration depend on prostate stem cell function, the delicate balance of stem cell self-renewal and differentiation. However, mechanisms modulating prostate stem cell function remain poorly identified. Here, we explored the roles of Yes-associated protein 1 (YAP) in prostate stem cells, prostate development and regeneration. Using YAPfl/fl, CD133-CreER mice, we found that stem cell-specific YAP-deficient mice had compromised branching morphogenesis and epithelial differentiation, resulting in damaged prostate development. YAP inhibition also significantly affected the regeneration process of mice prostate, leading to impaired regenerated prostate. Furthermore, YAP ablation in prostate stem cells significantly reduced its self-renewal activity in vitro, and attenuated prostate regeneration of prostate grafts in vivo. Further analysis revealed a decrease in Notch and Hedgehog pathways expression in YAP inhibition cells, and treatment with exogenous Shh partially restored the self-renewal ability of prostate sphere cells. Taken together, our results revealed the roles of YAP in prostate stem cell function and prostate development and regeneration through regulation of the Notch and Hedgehog signaling pathways.

Unveiling novel insights in prostate cancer through single-cell RNA sequencing.

Single-cell RNA sequencing (scRNA-seq) is a cutting-edge technology that provides insights at the individual cell level. In contrast to traditional bulk RNA-seq, which captures gene expression at an average level and may overlook important details, scRNA-seq examines each individual cell as a fundamental unit and is particularly well-suited for identifying rare cell populations. Analogous to a microscope that distinguishes various cell types within a tissue sample, scRNA-seq unravels the heterogeneity and diversity within a single cell species, offering great potential as a leading sequencing method in the future. In the context of prostate cancer (PCa), a disease characterized by significant heterogeneity and multiple stages of progression, scRNA-seq emerges as a powerful tool for uncovering its intricate secrets.

P300/SP1 complex mediating elevated METTL1 regulates CDK14 mRNA stability via internal m7G modification in CRPC.

BACKGROUND: N7-methylguanosine (m7G) modification is, a more common epigenetic modification in addition to m6A modification, mainly found in mRNA capsids, mRNA interiors, transfer RNA (tRNA), pri-miRNA, and ribosomal RNA (rRNA). It has been found that m7G modifications play an important role in mRNA transcription, tRNA stability, rRNA processing maturation, and miRNA biosynthesis. However, the role of m7G modifications within mRNA and its "writer" methyltransferase 1(METTL1) in tumors, particularly prostate cancer (PCa), has not been revealed. METHODS: The differential expression level of METTL1 between hormone-sensitive prostate cancer (HSPC) and castrate-resistant prostate cancer (CRPC) was evaluated via RNA-seq and in vitro experiments. The effects of METTL1 on CRPC progression were investigated through in vitro and in vivo assays. The upstream molecular mechanism of METTL1 expression upregulation and the downstream mechanism of its action were explored via Chromatin Immunoprecipitation quantitative reverse transcription polymerase chain reaction (CHIP-qPCR), Co-immunoprecipitation (Co-IP), luciferase reporter assay, transcriptome-sequencing, m7G AlkAniline-Seq, and mRNA degradation experiments, etc. RESULTS AND CONCLUSION: Here, we found that METTL1 was elevated in CRPC and that patients with METTL1 elevation tended to have a poor prognosis. Functionally, the knockdown of METTL1 in CRPC cells significantly limited cell proliferation and invasive capacity. Mechanistically, we unveiled that P300 can form a complex with SP1 and bind to the promoter region of the METTL1 gene via SP1, thereby mediating METTL1 transcriptional upregulation in CRPC. Subsequently, our findings indicated that METTL1 leads to enhanced mRNA stability of CDK14 by adding m7G modifications inside its mRNA, ultimately promoting CRPC progression.

[Corrigendum] CDCA5 promotes the progression of prostate cancer by affecting the ERK signalling pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the data panels showing the results of Transwell invasion assays (specifically, the 'C4­2 / shCON' and the PC­3 / CON panels) featured in Fig. 3F on p. 927 contained overlapping sections, such that data that were intended to show the results from differently performed experiments appeared to have been derived from the same original source. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 3, containing the correct representative image of the PC­3shCON group, is shown on the next page. The authors also noted that the statistics in Fig. 3G remained correct, and did not require correction on account of the error made in assembling this figure. Similarly, note that the correction made to this figure does not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 45: 921­932, 2021; DOI: 10.3892/or.2021.7920].

Post-transcriptional modification of m6A methylase METTL3 regulates ERK-induced androgen-deprived treatment resistance prostate cancer.

As the most common modification of RNA, N6-methyladenosin (m6A) has been confirmed to be involved in the occurrence and development of various cancers. However, the relationship between m6A and castration resistance prostate cancer (CRPC), has not been fully studied. By m6A-sequencing of patient cancer tissues, we identified that the overall level of m6A in CRPC was up-regulated than castration sensitive prostate cancer (CSPC). Based on the analysis of m6A-sequencing data, we found m6A modification level of HRas proto-oncogene, GTPase (HRAS) and mitogen-activated protein kinase kinase 2 (MEK2 or MAP2K2) were enhanced in CRPC. Specifically, tissue microarray analysis and molecular biology experiments confirmed that METTL3, an m6A "writer" up-regulated after castration, activated the ERK pathway to contribute to malignant phenotype including ADT resistance, cell proliferation and invasion. We revealed that METTL3-mediated ERK phosphorylation by stabilizing the transcription of HRAS and positively regulating the translation of MEK2. In the Enzalutamide-resistant (Enz-R) C4-2 and LNCap cell line (C4-2R, LNCapR) established in the current study, the ERK pathway was confirmed to be regulated by METTL3. We also found that applying antisense oligonucleotides (ASOs) to target the METTL3/ERK axis can restore Enzalutamide resistance in vitro and in vivo. In conclusion, METTL3 activated the ERK pathway and induced the resistance to Enzalutamide by regulating the m6A level of critical gene transcription in the ERK pathway.

TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2.

TEAD3 acts as a transcription factor in many tumors to promote tumor occurrence and development. But in prostate cancer (PCa), it appears as a tumor suppressor gene. Recent studies have shown that this may be related to subcellular localization and posttranslational modification. We found that TEAD3 was down-expressed in PCa. Immunohistochemistry of clinical PCa specimens confirmed that TEAD3 expression was the highest in benign prostatic hyperplasia (BPH) tissues, followed by primary PCa tissues, and the lowest in metastatic PCa tissues, and its expression level was positively correlated with overall survival. MTT assay, clone formation assay, and scratch assay confirmed that overexpression of TEAD3 could significantly inhibit the proliferation and migration of PCa cells. Next-generation sequencing results indicated that Hedgehog (Hh) signaling pathway was significantly inhibited after overexpression of TEAD3. Rescue assays suggested that ADRBK2 could reverse the proliferation and migration ability caused by overexpression of TEAD3. TEAD3 is downregulated in PCa and associated with poor patient prognosis. Overexpression of TEAD3 inhibits the proliferation and migration ability of PCa cells via restraining the mRNA level of ADRBK2. These results indicate that TEAD3 was down-expressed in PCa patients and was positively correlated with a high Gleason score and poor prognosis. Mechanistically, we found that the upregulation of TEAD3 inhibits the proliferation and metastasis of prostate cancer by inhibiting the expression of ADRBK2.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.

Characteristics of and antibiotic resistance in urinary tract pathogens isolated from patients with upper urinary tract stones.

To investigate the distribution characteristics and antibiotic resistance patterns of uropathogens in patients with upper urinary calculi and urinary tract infections, data on sex, age, positive midstream urine culture results and drug sensitivity results were collected. The statistical program SPSS 26.0 was used for statistical analysis. Among the 1414 positive urine samples, the most common pathogens were Escherichia coli (36.4%), Enterococcus faecalis (13.8%), Staphylococcus epidermidis (7.5%), Klebsiella pneumoniae (5.0%), Streptococcus agalactiae (3.4%) and Enterococcus faecium (3.3%). The incidences of E. coli (48.6%), K. pneumoniae (6.3%) and Proteus mirabilis (4.2%) were higher in female patients than in male patients (23.2%, 3.5%, 0.6%, respectively; P<0.05). E. faecalis was detected more frequently in the young group (16.0%) than in the elderly group (11.2%; P<0.01). Most of the isolates were resistant to levofloxacin and ciprofloxacin, while few were resistant to imipenem, meropenem, cefoperazone/sulbactam, piperacillin/tazobactam and amikacin. The bacterial spectra in patients with urinary stones varied by sex and age, which should be taken into consideration during treatment. The proportion of E. faecium showed an upward trend, while those of S. epidermidis and S. agalactiae demonstrated downward trends in the study period. Regardless, carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam and amikacin are good choices for serious cases.

Circular RNAs in Prostate Cancer: Is it Time to Further Explore Liquid Biopsies?

BACKGROUND: Although diagnosis and treatment of prostate cancer (PCa) have evolved rapidly in recent years, clinically significant molecular biomarkers are still needed to lower the mortality. Circular RNAs (circRNAs) are a poorly characterized component of PCa transcriptome. Recently, since the development of deep RNA sequencing and novel bioinformatic pipelines, emerging evidence suggests circRNAs to have diverse functions in the development and progression of PCa. Thus, we attempt to summarize the current situation and potential development prospects about the role of circRNAs in PCa liquid biopsies. METHODS: The role of circRNAs in PCa was summarized by searching the literature related to circRNAs in PubMed in recent years. RESULTS: Deregulation of circRNAs is associated with cell proliferation, apoptosis, cell invasion, migration, as well as metastasis in PCa. Because of the high stability and tissue specificity of circRNAs, with improved detection methodologies, circRNAs may be predictive biomarkers in liquid biopsies. CONCLUSION: From the perspective of recent research, with the development of high-throughput sequencing and novel bioinformatics tools, knowledge of circRNAs will be further expanded. Improved technologies will make personalized precision medicine less of a paper exercise. It is time to further explore circRNA in liquid biopsies.

Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer.

BACKGROUND: Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. We also investigate the functions of some specific exosome biomarkers in the progression of CRPC. METHODS: Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models. RESULTS: Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. CONCLUSION: Integration of proteomics and metabolomics data generated proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression.

Androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation of prostate cancer.

Androgen receptor (AR) plays an important role in the progression of prostate cancer and has been targeted by castration or AR-antagonists. The emergence of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) is inevitable. However, it is not entirely clear how ADT fails or how it causes resistance. Through analysis of RNA-seq data, we nominate ARHGEF2 as a pivotal androgen-repressed gene. We show that ARHGEF2 is directly suppressed by androgen/AR. AR occupies the enhancer and communicates with the promoter region of ARHGEF2. Functionally, ARHGEF2 is important for the growth, lethal phenotype, and survival of CRPC cells and tumor xenografts. Correspondingly, AR inhibition or AR antagonist treatment can restore ARHGEF2 expression, thereby allowing prostate cancer cells to induce treatment resistance and tolerance. Overall, our findings provide an explanation for the contradictory clinical results that ADT resistance may be caused by the up-regulation of ARHGEF2 and provide a novel target.

Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.

BACKGROUND: While immunotherapy has shown potent efficacy in clinical practices, patient selection to receive checkpoint blockade is still challenging in prostate cancer (PCa). LAT and ZAP70 functions in lymphocyte activation and plays a critical role in T cell receptor (TCR) signal transduction. However, PCa genomic and clinical data regarding the role of LAT and ZAP70 are limited. We aim to identify and characterize LAT/ZAP70 defined subtypes of PCa. METHODS: We elaborated the TCGA PCa data and metastatic castration-resistant prostate cancer (mCRPC) RNA-seq data bioinformatic analysis and systematically elucidated the role of intra-tumoral expressed LAT and ZAP70 in the progression-free survival and immunotherapeutic-related signals. LAT/ZAP70-associated immune infiltration was evaluated using bioinformatic tools. Immunohistochemical staining of serial sections was used to confirm the expression and distribution of LAT, ZAP70 and androgen receptor (AR) in PCa tissues. RESULTS: Specifically, LAT and ZAP70 revealed increased expressions in PCa when compared to normal tissues and positively associated with intra-tumoral immune cells infiltration. LAT/ZAP70 defined immune-high early-stage PCa revealed higher TP53 mutation frequency and poor prognosis. Transcriptome analysis indicated immune-related signals and CTLA4 expression were highly enhanced in immune-high PCa parallel with higher protein level of MYC and lower AR expression. In mCRPC, LAT/ZAP70 defined immune-high patients also revealed upregulated immune related signals, higher CTLA4 expression and DNA repair deficiency. CONCLUSION: LAT/ZAP70 defined immune-high PCa linked to immune infiltration and predicts poor prognosis. Immune-high PCa may receive effective response from immune checkpoint inhibitor parallel with systemic treatment.

YAP1-TEAD1 mediates the perineural invasion of prostate cancer cells induced by cancer-associated fibroblasts.

Perineural invasion (PNI) driven by the tumor microenvironment (TME) has emerged as a key pattern of metastasis of prostate cancer (PCa), while its underlying mechanism is still elusive. Here, we identified increased CAFs and YAP1 expression levels in patients with metastatic PCa. In the cultured PCa cell line LNCaP, co-culture with cancer-associated fibroblasts (CAFs) could upregulate YAP1 protein expression. Either ectopic overexpression of YAP1 or co-culture with CAFs could promote the infiltration of LNCaPs towards dorsal root ganglia (DRG). This effect could be blocked using an YAP1 inhibitor. In vivo, overexpression of YAP1 could increase PNI in a mouse model of sciatic nerve tumor invasion. Mechanistically, TEAD1 binds to the NGF promotor and YAP1/TEAD1 activates its transcription and consequently increases NGF secretion. In turn, PCa cells treated with CM from CAFs or stable YAP1 overexpression can stimulate DRG to secrete CCL2. The epithelial-to-mesenchymal transition (EMT) of PCa cells is thus activated via CCL2/CCR2. Overall, our data demonstrate that CAFs can activate YAP1/TEAD1 signaling and increase the secretion of NGF, therefore promoting PCa PNI. In addition, EMT induced by PNI suggests a feedback loop is present between neurons and PCa cells.

hsa_circ_0092339 acts as a molecular sponge in castration-resistant prostate cancer via the hsa-mir-940/C-MYC axis.

Aims: We aimed to determine whether intronic circRNA acts as a molecular sponge in castration-resistant prostate cancer (CRPC). Materials & methods: A gene chip technique was used to conduct sequencing. A qPCR experiment was performed to verify the result. Radioimmunoprecipitation, RNA pull-down and dual-luciferase reporter assays were performed to particularly expound its function. Verification of downstream effects was carried out through qPCR and western blot, and a xenograft assay was performed in vivo for verification. Results: Intronic circRNA hsa_circ_0092339 in the nucleus was highly expressed in CRPC cell lines. hsa_circ_0092339 did not regulate the expression of its parental gene. hsa_circ_0092339 functions like a molecular sponge, preventing degradation of C-MYC mRNA by absorbing hsa-mir-940. Conclusion: hsa_circ_0092339 plays a critical role in CRPC through targeting C-MYC indirectly by absorbing hsa-mir-940.

Our research breaks the mold by investigating a novel function of RNA and a novel regulatory mechanism. Our research provides a new therapeutic target for prostate cancer treatment and broadens the understanding of prostate cancer.

One-Stage Flexible Ureteroscopy during Single-Tract Percutaneous Nephrolithotomy in the Treatment of Parallel Calyceal Stones.

INTRODUCTION: The aim of this study was to compare the clinical safety and efficiency between one-stage flexible ureteroscopy (FURS) during single-tract percutaneous nephrolithotomy (PCNL) and multi-tract PCNL in the treatment of parallel calyceal stones. METHODS: One hundred and twenty-five patients who had calyceal stones parallel to puncture channel from March 2017 to January 2021 were enrolled and assigned into two groups. Seventy cases received the treatment of FURS combined with single-tract PCNL under the oblique supine position (the Combined group), and 55 cases had multi-tract PCNL procedure under the prone position (the Multi-tract group). Demographic characteristics, clinical information, and surgical outcomes were analyzed. RESULTS: Demographic variables and stone characteristics did not show statistical difference between the two groups. Compared with the Multi-tract group, there were longer operation time (p = 0.021), shorter postoperative hospitalization days (p = 0.003), smaller postoperative hemoglobin drop (p = 0.002), less incidence of moderate and severe postoperative pain (p = 0.001), and postoperative perirenal hematoma (p = 0.012) in the Combined group. No significant difference was found in the stone-free rate (SFR) and postoperative fever between the two groups (p = 0.880 and p = 0.324). More patients needed postoperative intervening embolization in the Multi-tract group (p = 0.048). DISCUSSION/CONCLUSIONS: For most patients with parallel calyceal stones, one-stage FURS combined with single-tract PCNL procedure was a safer procedure for the reduction of complications and could achieve a comparative SFR compared to the multi-tract PCNL.

The cell cycle gene centromere protein K (CENPK) contributes to the malignant progression and prognosis of prostate cancer.

Background: The cell cycle gene centromere protein K (CENPK) is upregulated in various cancers; however, the clinical value and mechanism of CENPK in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) remain unclear. Methods: The expression of CENPK in PCa was analyzed in both patients with PCa and cell lines using immunohistochemistry (IHC), real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and bioinformatics analyses. Knockdown of CENPK in PCa cells was achieved by transfecting siRNAs and assessed using qRT-PCR and Western blotting. MTT and colony formation assays were used to assess the growth of PCa cells. The cell cycle was analyzed using propidium iodide (PI) staining and flow cytometry. To study the possible biological function of CENPK, pathway enrichment analysis was performed by dividing these groups into a high CENPK expression group and a low CENPK expression group based on the median CENPK expression level. Finally, the correlation between CENPK expression in PCa and clinical parameters was evaluated. Results: Our study revealed that CENPK was expressed at high levels in CRPC tissues and cell lines compared to primary PCa. The downregulation of CENPK significantly inhibited cell viability and reduced the number of colonies formed by LNCaP-AI and DU145 cells (two CRPC cell lines). Gene enrichment and flow cytometry analyses showed that high CENPK expression was linked to mitotic spindles and the cell cycle and may be involved in mitosis in the cell cycle of cancer cells to modulate cell proliferation and promote the development of CRPC. Moreover, patients exhibiting higher expression of the CENPK mRNA experienced shorter disease-free survival (DFS) and overall survival (OS) than the lower expression group. Conclusions: This study provides novel molecular insights into the role of CENPK in castration-resistant PCa cells and reveals that an increase in CENPK expression may indicate shorter DFS and a poor prognosis for patients with PCa. Targeting CENPK may be a novel strategy for the treatment of PCa.