BACKGROUND:Penile squamous cell carcinoma (pSCC) severely impairs quality of life, yet reliable prognostic factors for lymph node metastasis (LNM) and survival remain incompletely defined. Existing LNM detection is invasive and risky, while prior TP53/p53-related pSCC studies are limited by small samples and conflicting results. METHODS:We analyzed p53 protein expression via IHC in a single-center retrospective pSCC cohort, combined with a systematic review and meta-analysis to validate TP53/p53 alterations' prognostic value for LNM, overall survival (OS), and cancer-specific survival (CSS). RESULTS:In our single-center cohort, p53 mutant-pattern expression was associated with increased LNM risk (OR = 7.56, 95%CI = 1.48-38.52), inferior OS (HR = 6.15, 95%CI = 1.78-21.13), and poorer CSS (HR = 7.92, 95%CI = 1.99-31.45). These nominally significant associations with wide confidence intervals highlight the need for large-scale investigations; accordingly, we conducted a meta-analysis confirming that aberrant p53/TP53 status correlates with elevated LNM (pooled OR = 2.90, 95%CI = 1.89-4.44), inferior OS (pooled HR = 1.79, 95%CI = 1.31-2.44), and shorter CSS (pooled HR = 2.90, 95%CI = 1.55-5.42). CONCLUSIONS:TP53 genetic status and p53 protein expression are consistently associated with LNM and survival outcomes, supporting a prognostic role in penile squamous cell carcinoma (pSCC). These associations are validated in a Chinese pSCC cohort and further quantify via comprehensive meta-analysis in this understudied rare malignancy. These findings highlight the potential of TP53/p53 assessment to inform future personalized management strategies for pSCC, pending formal validation of its clinical utility. IMPACT:This study, integrating a single-center Chinese cohort validation with the first multi-source pooled analysis jointly quantifying the prognostic value of both TP53 genetic status and p53 protein expression in pSCC, addresses the critical gap of insufficient high-powered, integrated evidence for this potential prognostic biomarker, provides a consolidated evidence base for risk stratification in this rare malignancy, and informs the design of subsequent prospective validation studies.

The basic clinical information of the human specimens analyzed in the manuscript

Zinner syndrome is a rare congenital malformation of the male genitourinary system, characterized by a triad: seminal vesicle cyst, unilateral renal agenesis, and ipsilateral ejaculatory duct obstruction. The etiology of this uncommon disease remains largely elusive; however, genetic mutations may contribute to its development. In this report, we present a case of symptomatic Zinner syndrome that was surgically treated, alongside an investigation into the potential genetic basis of the syndrome via whole exome sequencing. We report the case of an 18-year-old male presenting with urinary pain and was diagnosed with right renal agenesis and a left seminal vesicle cyst following comprehensive imaging. The patient also experienced perineal pain and urgency, without symptoms of frequent urination, dysuria, or hematuria, and no familial history of genitourinary anomalies was documented. He successfully underwent laparoscopic resection of a pelvic mass, with pathological examination confirming a seminal vesicle cyst. Postoperative recovery was uneventful. Whole exome sequencing of blood and tissue samples highlighted myeloma overexpressed gene (MYEOV), B melanoma antigen family member (BAGE), and N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) as potential mutated genes related to Zinner syndrome. Additionally, two predisposing genetic variants were identified. Zinner syndrome is a rare condition commonly diagnosed via various imaging modalities. Surgical resection remains the most effective treatment for symptomatic cases. Gene sequencing provides valuable insights into the genetic etiology of Zinner syndrome, enhancing our understanding and potentially guiding future diagnostic approaches.

Supplementary data related to Figure 3

The levels of MLYCD expression and Ran K141 malonylation correlates with the clinical prognosis of PCa patients

Primary renal mucosa-associated lymphoid tissue (MALT) lymphoma is exceedingly rare. Although immune thrombocytopenia (ITP) may accompany lymphoproliferative disorders, its association with primary renal MALT lymphoma has not been previously reported. A 60-year-old male presenting with isolated thrombocytopenia was diagnosed with ITP during hematologic evaluation. Abdominal imaging incidentally revealed an 8.7 × 5.6 cm renal mass. Glucocorticoid therapy successfully stabilized platelet counts, enabling nephroureterectomy. Histopathological analysis demonstrated dense small lymphocyte infiltrates, with immunohistochemical confirmation of CD20 and Bcl-2 positivity establishing a diagnosis of MALT lymphoma. At six-month follow-up, the patient maintained disease-free status without adjuvant therapy. We report a rare case of concurrent primary renal MALT lymphoma and ITP, achieving sustained remission through glucocorticoid therapy and surgical resection.

Background:Tumor heterogeneity impacts invasive behaviors, treatment response, and clinical outcomes in triple-negative breast cancer (TNBC). However, this heterogeneity remains incompletely characterized. This study aims to utilize multi-scale data to investigate inter-tumoral heterogeneity and identify potential TNBC biomarkers. Methods:Single-cell RNA expression profiles were analyzed using R packages. Specifically, the infercnv, Pyscenic, GeneNMF, SCP, Vector, CellChat, and hdWGCNA packages were employed to identify malignant cells and characterize heterogeneity in transcription factors, metaprograms, lineage evolution, developmental trajectories, cell-cell interactions, and co-expression networks. Bulk RNA datasets were incorporated to assess the prognostic value of cell clusters and candidate genes. G Protein Subunit Alpha 15 (GNA15) expression was determined via reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. Cell functional assays were performed to evaluate proliferation, migration, and invasion capabilities. Results:A total of 14,335 malignant cells were isolated from epithelial cells across 15 single-cell RNA samples. Six tumor cell clusters were identified, which exhibited distinct prognoses, biological functions, driver transcription factors, and co-expression networks. Notably, the S2 cluster demonstrated association with multiple malignancy-related pathways and inferior survival outcomes. GNA15 emerged as the S2 cluster hub gene. In vitro experiments confirmed that GNA15 knockdown significantly attenuated proliferation, migration, and invasion in TNBC cell lines. Conclusions:Our study comprehensively delineated TNBC tumor cell heterogeneity and established the critical role of GNA15 in TNBC progression. These findings enhance the understanding of TNBC heterogeneity and provide a theoretical foundation for TNBC treatment.

Ran K141 malonylation promoted AR nuclear localization, related to Figure 5

MLYCD decreased the levels of Ran K141 malonylation, related to Figure 4

Restoration of MLYCD expression depleted intracellular malonyl-CoA to repress lipid accumulation and activat PERK mediated endoplasmic reticulum stress signaling pathways

ObjectiveBreast cancer remains the leading cause of cancer-associated death for women globally. For the group of ER+ breast cancer patients, there are still some problems of poor prognosis that need to be solved. This study aims to identify the poor prognostic tumor subgroups for the prognostic stratification of ER+ patients.MethodsThrough a comprehensive multi-omics strategy, we systematically characterized the biological and clinical significance of MUCL1+CD24+ cells in breast cancer, and we used multiplex immunohistochemistry to confirm the poor role of MUCL1+CD24+ cells.ResultsSingle-cell transcriptomics unraveled the cellular ontogeny and immune microenvironment interactions of this subset, while bulk RNA sequencing exposed significant pathway heterogeneity and differential immunotherapy responses associated with varying cellular abundance levels. Genomic landscape analysis pinpointed specific somatic mutations correlated with MUCL1(+) CD24(+) cell infiltration patterns, findings that were subsequently validated through multiplex immunohistochemistry to demonstrate strong prognostic value. Crucially, we developed a clinically translatable radiomics approach that successfully correlated specific MRI features with cellular prevalence, establishing a foundation for noninvasive detection of this aggressive cellular subpopulation.ConclusionsThis integrative approach, spanning molecular to imaging analyses, provides novel insights into both the biological drivers and clinical implications of MUCL1(+) CD24(+) cells in breast cancer progression.

Malonyl-CoA, a key metabolite, is not only the building block for lipogenesis but also a critical regulator of mitochondrial fatty acid β-oxidation. Given the altered metabolic state of many cancers, malonyl-CoA may play a role in tumor development and drug resistance, especially in malignancies characterized by abnormal lipid metabolism, such as prostate cancer. In this study, we showed that the levels of malonyl-CoA were increased in prostate cancer, especially in castration-resistant prostate cancer. Abnormal accumulation of malonyl-CoA promoted lipogenesis and regulated metabolic processes, maintaining endoplasmic reticulum homeostasis and mitochondrial function and ultimately contributing to prostate cancer progression. Restoration of malonyl-CoA decarboxylase expression activated the unfolded protein response via the consumption of malonyl-CoA. Importantly, malonyl-CoA accumulation promoted lysine malonylation in prostate cancer. Ran K141 malonylation increased Ran activity and enhanced androgen receptor nuclear translocation and transcriptional activity, ultimately contributing to prostate cancer development and resistance to antiandrogens. These findings highlight the function of malonyl-CoA in prostate cancer progression by regulating metabolic processes and malonylating Ran K141, revealing that the malonyl-CoA axis might be a reliable biomarker and a potential therapeutic target in prostate cancer. Significance: Malonyl-CoA induces metabolic reprogramming and Ran-mediated androgen receptor activation to support prostate cancer development and drug resistance, providing a mechanism that could be harnessed for developing treatment strategies for advanced prostate cancer.

Supplementary data related to Figure 1-2

Restoration of MLYCD reversed resistance to ENZ in PCa, related to Figure 7

Long-segment proximal ureteral strictures present a significant surgical challenge, particularly in patients unwilling or unsuitable for an oral mucosal graft. Here we report the first series of laparoscopic ureteroplasty procedures with a spliced appendiceal mucosal graft (SAMG) for proximal ureteral stricture. The novel technique was performed successfully in all three patients without conversion to open surgery. The mean operative time was 178.3 min, mean estimated blood loss was 36.7 ml, and mean hospital stay was 5.6 d. The postoperative follow-up period was at least 12 mo, and all patients exhibited a reduction in hydronephrosis and no obstruction of the reconstructed ureteral segments. There were no major intraoperative or postoperative complications. SAMG ureteroplasty appears to be a safe and effective surgical method for repair of proximal ureteral stricture.

Ran K141 malonylation increased the AR transcriptional activity in PCa cells

To evaluate the safety and feasibility of intraperitoneal laparoscopic surgery in Trendelenburg position (ILSTP) for pyelolithotomy, pyeloplasty, and heminephrectomy in patients with horseshoe kidneys (HSKs). Between March 2021 and March 2024, three patients with HSKs underwent ILSSP. Of these three patients, two with pelvi-ureteric junction obstruction with recurrent kidney stones underwent pyelolithotomy and pyeloplasty, one with symptomatic nonfunctioning left moiety of a HSK was managed with heminephrectomy. Mean operating time was 114 ± 64.8 (44–172) min, and estimated blood loss was 63.3 ± 51.3 (20–120) ml. The mean hospital stay was 3.3 ± 1.5 (2–5) days. There were no major intra- or post-operative complications. ILSTP is a feasible and effective technique for performing pyelolithotomy, pyeloplasty, and heminephrectomy in patients with HSKs.