Background: Prostate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa. Methods: Cuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4.Results: Two cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription.Conclusion: The cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.

Background: Poly(A) binding protein cytoplasmic 4 (PABPC4) has been regarded as a prognostic marker in many malignancies. In this study, we evaluated PABPC4 expression at both messenger ribonucleic acid (mRNA) and protein levels. The prognostic value of PABPC4 in patients with prostate cancer (PCa) was also investigated. Methods: The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, our analysis of Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), and 65 pairs of ribonucleic acid (RNA) sequencing data from our center were employed to detect the expression of PABPC4 in PCa tissues. Tissue microarrays (TMAs) were utilized to detect the expression of the PABPC4 protein, and survival analysis as well as risk factor analysis were conducted. Results: In the 65 pairs of sequencing data, the expression of PABPC4 in tumor tissues was significantly higher than that in paired adjacent tissues (P<0.001), and its expression also presented significant differences among different Gleason groups (P=0.041). In the CPGEA data, the expression of PABPC4 in tumor tissues was significantly higher than that in control tissues (P<0.001), and the expression of PABPC4 in M1 patients was higher than that in M0 patients, although no significant statistical difference was shown (P=0.051). In the TCGA data, the expression of PABPC4 in tumor tissues was significantly higher than that in control tissues (P<0.001). The expression of pT3/4 (pathological tumor stage 3 and pathological tumor stage 4) in high-stage tumor tissues was significantly higher than that in low-stage tumor tissues (pT2) (P=0.02), the expression of pT3/4 in GSE21034 and GSE32571 tumor tissues was significantly higher than that in control tissues (P<0.001), and the expression of pT3/4 in primary tumor tissues was higher than that in metastatic tissues in GSE6752 (P<0.001). The TCGA data revealed that patients with high PABPC4 expression had poorer overall survival (OS) than those with low PABPC4 expression (P=0.04), and the TMA data indicated that patients with high PABPC4 expression had a poor prognosis (P=0.004). Conclusions: Our study demonstrated that PABPC4 was overexpressed at mRNA and protein levels in PCa. We found that patients with high PABPC4 expression had a shorter biochemical recurrence (BCR)-free survival and OS, showing its value as a prognostic biomarker in patients with PCa.

Penile metastasis from prostate cancer is rare and is associated with a poor prognosis; however, there is currently a lack of high‐level evidence to guide the management of this condition. This case report describes a 68‐year‐old male with prostate cancer who developed a penile metastasis during follow‐up. This occurred despite stable prostate‐specific antigen (PSA) levels after treatment with androgen deprivation therapy, combined with endocrine therapy and radiotherapy. Imaging studies and intraoperative frozen section pathology suggested a penile tumor. The patient subsequently underwent total penectomy combined with urinary diversion surgery. Postoperative histopathology confirmed poorly differentiated adenocarcinoma consistent with metastatic prostatic adenocarcinoma exhibiting morphological changes related to prior therapy. This case highlights the importance of maintaining clinical suspicion for penile metastasis in prostate cancer patients with stable PSA levels, especially in the context of tumor dedifferentiation, to facilitate early diagnosis and appropriate intervention.

Background: Pelvic lymph node dissection (PLND) is regarded as a crucial component of radical prostatectomy (RP); however, it also increases the probability of postoperative complications. This study aimed to investigate the significance of PLND in the treatment of prostate cancer. Methods: A total of 1,474 patients with complete clinical data were retrospectively analyzed. Multivariable logistic regression analysis was used to identify the factors of PLND and lymph node metastasis (LNM). Propensity score matching (PSM) was performed to balance baseline characteristics between patients in different groups, along with Kaplan-Meier survival analysis to explore the impact of PLND on oncological outcomes. Results: Of the 1,474 patients, 956 (64.9%) underwent PLND, and 159 (16.6%) had LNM. The positive rate of lymph nodes in the extended PLND (ePLND) group was higher than that in the obturator resection group (20.58% vs. 10.05%, P<0.001). Multivariable Logistic regression showed that age, serum prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade, clinical T stage and risk stratification were correlated with PLND during RP (P<0.05); ISUP grade, clinical T staging and risk stratification increased the risk of LNM (P<0.05). After PSM, patients in RP group had similar survival compared to the PLND group (P=0.80); the ePLND group and obturator resection group also achieved equivalent survival (P=0.16). Among lymph node-positive patients, the disease progression-free survival in the adjuvant therapy group seemed superior to the non-adjuvant therapy group (P<0.001); and the adjuvant therapy group had better survival than those without PLND (P=0.02). Conclusions: ePLND is recommended for patients with indications of lymphadenectomy, which can significantly optimize the detection rate of positive lymph nodes and provide guidance for subsequent adjuvant therapy.