Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with malignant potential, affecting various anatomical regions, predominantly the head and neck. Urogenital involvement is relatively uncommon. In particular, penile neurofibromatosis is exceedingly rare, with fewer than 20 cases documented globally. In China, only four pediatric cases have been reported, with no known occurrences in adults. To date, no recurrent penile plexiform neurofibromas have been reported in adults. Here, we report a rare case of a recurrent giant penile plexiform neurofibroma, accompanied by multiple neurofibromas involving the prostate, bladder, and retroperitoneum, in an adult NF1 patient.

A 37-year-old male patient initially presented to the Department of Urology, Shandong First Medical University Affiliated Provincial Hospital, on April 17, 1994 (at the age of 8), with a seven-year history of painless penile enlargement. He underwent resection of the penile mass, with histopathological analysis confirming a diagnosis of plexiform neurofibroma. Following surgery, the penile morphology normalized. However, at the age of 20, he experienced recurrent painless penile enlargement but did not pursue further medical evaluation. On October 7, 2023, the patient was readmitted due to right flank pain and hydronephrosis. Physical examination revealed marked penile enlargement with a palpable large mass and multiple café-au-lait macules across the body. Although the patient had no urinary complaints, he was unable to achieve normal erectile function. Laboratory findings indicated an elevated serum creatinine level of 124.20 µmol/L. Imaging modalities, including computed tomography urography (CTU), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT), identified a massive penile tumor with concomitant multiple tumors in the prostate, bladder, and retroperitoneum. Penile tumor biopsy confirmed the diagnosis of plexiform neurofibroma. Immunohistochemical analysis demonstrated S-100 (+), recombinant human SOX10 protein (SOX10) (+), and Ki-67+ (< 1%). Given the histopathological results and clinical findings, the patient was diagnosed with neurofibromatosis type 1. To alleviate right flank pain, percutaneous nephrostomy was performed, resulting in a reduction in serum creatinine to 90.80 µmol/L within three days post-procedure, with subsequent symptom relief. Owing to extensive tumor infiltration and financial limitations, the patient opted against radical surgery or systemic therapy. He was subsequently discharged and has since been monitored with biannual follow-ups, including regular nephrostomy tube replacement. As of the latest follow-up, his clinical status remains stable without evidence of significant disease progression.

This case report describes a rare adult patient with neurofibromatosis type 1, presenting with recurrent giant penile plexiform neurofibroma accompanied by multiple neurofibromas involving the prostate, bladder, and retroperitoneum. To the best of our knowledge, this combination of manifestations represents the first reported case. The patient underwent only percutaneous nephrostomy to alleviate symptoms, without pursuing additional treatment. Follow-up evaluations indicated a stable clinical course, suggesting that certain NF1 patients may achieve long-term stability without aggressive therapeutic intervention. This case underscores the importance of comprehensive evaluation, prolonged surveillance, and multidisciplinary management for NF1 patients, particularly those with extensive and atypical disease manifestations. Treatment decisions should consider a balance between patient preferences and the natural progression of the disease. This report offers valuable insights into the management of similar cases.

Progress in molecular medicine has resulted in novel cancer therapies, with microRNAs (miRNAs) recognized as promising instruments for cancer detection and treatment. MicroRNAs are tiny non-coding RNA sequences that manipulate gene expression at the post-transcriptional stage and are involved in cellular differentiation and death. miR-32-5p demonstrates oncogenic activity in several cancers, while c-MYC oncogene is a well-known driver of cancer, promoting tumor growth by stimulating cell proliferation, blocking apoptosis, and suppressing immune responses. This study aimed to examine how inhibiting miR-32-5p affected the behavior of breast tumor cells (MCF-7), particularly focusing on changes in cellular apoptosis and proliferation, and to investigate its relationship with c-MYC expression. A locked nucleic acid (LNA)-based inhibitor was used to knock down miR-32-5p in MCF-7 breast cancer cells. Cell viability was assessed using MTT assays at 24, 48, and 72 h post-transfection. Apoptotic and necrotic cell populations were differentiated using Annexin-V labeling with Propidium iodide. Expression levels of miR-32-5p and c-MYC were evaluated using quantitative Real-Time PCR before and after transfection with the miR-32-5p inhibitor. Inhibition of miR-32-5p significantly reduced MCF-7 cell viability at 48 h post-transfection (P < 0.002) and increased apoptotic cells to approximately 17% (vs. 0.3% in controls, P < 0.05), concomitant with significant downregulation of c-MYC mRNA (P < 0.006). The lowest level of miR-32-5p expression was observed at 48 h following transfection, with levels gradually increasing by 72 h. This study is the first to demonstrate a plausible regulatory relationship between miR-32-5p and c-MYC in breast tumor cells. The significant reduction in cell viability and increase in apoptosis following miR-32-5p inhibition, likely mediated through c-MYC downregulation, suggests a plausible pathway that may be targeted for therapeutic intervention in breast cancer.

This study aims to elucidate the complex molecular and cellular landscape of pancreatic ductal adenocarcinoma (PDAC) by identifying key regulatory non-coding RNAs (ncRNAs), hub protein-coding genes, and Intercellular communication pathways that may serve as prognostic biomarkers and therapeutic targets.

Pancreatic cancer remains one of the deadliest malignancies worldwide, characterized by late diagnosis, limited treatment response, and poor prognosis. Among its histological subtypes, PDAC accounts for over 80% of cases and is defined by a highly fibrotic and immunosuppressive tumor microenvironment (TME).

We performed a comprehensive bioinformatics analysis integrating multiple transcriptomic datasets from the NCBI Gene Expression Omnibus (GEO), including mRNA, miRNA, lncRNA, and circRNA profiles from PDAC and adjacent normal tissues. Differential expression analysis was conducted using GEO2R, followed by functional enrichment via DAVID. Hub genes were identified from protein-protein interaction (PPI) networks constructed using STRING and validated using GEPIA2. A competing endogenous RNA (ceRNA) network was developed to investigate regulatory ncRNA-mRNA axes. To refine these findings, single-cell RNA-seq (scRNA-seq) data were analyzed to resolve the cellular origin of hub genes and ncRNAs, and CellChat was employed to model intercellular communication within the TME.

We identified several dysregulated genes and ncRNAs implicated in key oncogenic pathways, including ECM remodeling, inflammation, and immune evasion. The ceRNA network highlighted functional interactions between circRNAs, lncRNAs, and miRNAs regulating key hub genes. Single-cell analysis revealed cell-type-specific expression of hub genes-e.g., FN1 and COL11A1 in fibroblasts, CXCL8 in macrophages, and ITGA3 in ductal cells-and uncovered a macrophage-endothelial CXCL8-ACKR1 signaling axis potentially driving tumor-associated angiogenesis. Moreover, correlations with immune cell infiltration and drug sensitivity further underscored the translational relevance of the identified molecular targets.

Our analysis combining bulk and single-cell transcriptomics provides a multi-scale view of PDAC pathogenesis. The findings highlight the interplay between ncRNAs, hub genes, and cellular crosstalk in shaping the tumor ecosystem and suggest novel targets for precision therapeutic intervention and biomarker development.

Gasdermin D (GSDMD), an effector molecule of cell pyroptosis, is known to be activated in various cells during inflammation. However, the patterns of GSDMD activation in immune regulatory cells such as myeloid-derived suppressor cells (MDSCs) remain unclear. In this study, we found that neutrophils in colorectal cancer (CRC) tissues exhibited reduced GSDMD transcription, as evidenced by a single-cell RNA sequencing result. Consistent with this, cleaved GSDMD expression is negatively correlated with S100A8 in CRC tissues. Additionally, CD15⁺CD14^-LOX1⁺ cells (G-MDSCs) from the peripheral blood of CRC patients exhibited a significant reduction in GSDMD activation. Mice with ubiquitous GSDMD deficiency bred in a clean environment exhibited a notable increase in G-MDSCs. These GSDMD^-/- MDSCs enhanced immunosuppressive activity by both inhibiting effector T-cell activity and promoting regulatory T-cell induction. This enhancement was also observed in GSDMD^flox/flox-S100A8^Cre mice, in which GSDMD was specifically deleted in MDSCs. The tumor-promoting effects in the GSDMD^-/- and GSDMD^flox/flox-S100A8^Cre mice were abrogated following MDSC depletion, as shown by the use of an anti-DR5 antibody. In the absence of GSDMD, G-MDSCs showed reduced inflammasome activation and decreased production of IL-1β and IL-18. Furthermore, a significant reduction in interferon-related factor 8/7 (IRF8/7) was observed in GSDMD^-/- G-MDSCs via bulk RNA sequencing analysis. After treatment with LPS/nigericin, these cells maintained mitochondrial integrity, thus impairing the mtDNA release and the downstream cGAS/STING/TBK1/IRF8/7 signaling axis activation. Reduced IRF8/7 levels were responsible for increased differentiation of GSDMD^-/- G-MDSCs. Finally, treatment with a GSDMD recombinant lentivirus injected into in situ tumors significantly inhibited tumor growth and reduced G-MDSC levels, suggesting that a GSDMD-based vaccine could simultaneously exert anti-carcinoma and anti-MDSC effects.

Cancer represents a significant global health hazard marked by elevated morbidity and mortality rates. Furthermore, the majority of tumor therapies encounter challenges, including metastasis, recurrence, and drug resistance. Consequently, it is essential to identify a specific and efficient tumor treatment approach. In recent years, the ongoing investigation and comprehension of tumors have led to significant attention towards cancer stem cells (CSCs). CSCs can facilitate tumor progression via self-renewal, differentiation capabilities, and multidrug resistance. Their function as a fundamental contributor to tumor heterogeneity, drug resistance, recurrence, and metastasis has emerged as a significant focus in cancer therapy research. In recent years, microRNAs (miRNAs) have been identified as crucial post-transcriptional regulators in biological processes, including chemosensitivity, self-renewal, apoptosis, invasion, and metastasis of cancer stem cells (CSCs). This paper systematically reviews the molecular mechanisms through which miRNAs influence the characteristics of cancer stem cells by targeting essential genes (e.g., SOX2, EGFR, c-Met) and modulating signaling pathways, including Wnt/β-catenin, Notch, Hedgehog, and PI3K/Akt. Furthermore, we investigated the viability of miRNAs as non-invasive biomarkers for cancer diagnosis and prognosis evaluation, examined the similarities and attributes of pivotal miRNAs in modulating cancer stem cell functionality, and deliberated on therapeutic approaches stemming from miRNA regulation of cancer stem cell activity. We anticipate that this research will yield novel insights into targeted cancer therapy.

This study aimed to clarify the alterations in gene expression in metastatic renal cell carcinoma (mRCC) during disease progression and in response to treatment with immune checkpoint inhibitors using a syngeneic mouse mRCC model. RENCA cells were orthotopically implanted in BALB/c mice. Mice received first-line treatment with cabozantinib, anti-PD-1 antibody, or a combination. Tumor progression was monitored using serial micro-computed tomography. Lung metastasis samples were collected, and RNA sequencing was performed. Mice with apparent disease progression received second-line treatment with axitinib, everolimus, or lenvatinib after combination therapy. The median overall survival was 28, 34, 34, and 49 days in untreated mice and those treated with cabozantinib, anti-PD-1, or their combination, respectively (p < 0.05). RNA sequencing revealed upregulation of the fibroblast growth factor pathway in lung metastases after monotherapy, whereas mTOR pathway activation was observed only after combination therapy. Treatment-specific gene expression changes occur in mRCC, suggesting that the optimal target for sequential therapy in mRCC varies depending on prior treatment.

WD repeat and SOCS box containing 2 (WSB2) is an E3 ubiquitin ligase that might be involved in regulating protein stability, thus performing important roles in the development of different types of cancer. However, the biological significance of WSB2 in pan‑cancer is unclear. Pan‑cancer analysis with the online platforms UALCAN and TIMER2.0. revealed that the expression levels of WSB2 were increased in various types of tumors, including breast invasive carcinoma, uterine corpus endometrial carcinoma, liver hepatocellular carcinoma and were decreased in other types such as colon adenocarcinoma, kidney chromophobe and rectum adenocarcinoma, compared with that in their corresponding normal tissues. In addition, pan‑cancer analysis using The Human Protein Atlas database indicated that WSB2 expression levels vary across different cancer types. Reverse transcription‑quantitative PCR (RT‑qPCR) revealed that WSB2 expression varied in 11 different cell lines. Promoter activity analysis indicates that specificity protein 1 carries out a key role in regulating WSB2 expression by binding to its promoter region. UALCAN and Kaplan‑Meier analysis were used to assess the pathological stage and prognostic value of WSB2 in pan‑cancer. Finally, overexpression of WSB2 promoted the proliferation and migration of MCF‑7 and MDA‑MB‑231 cells. Western blotting revealed that WSB2 increased the levels of vimentin, Snail and ERK1/2, and inhibited the expression of p53 and E‑cadherin in MDA‑MB‑231 and MCF‑7 cells. Transcriptome sequencing analysis identified 118 differentially expressed genes associated with WSB2 overexpression, which were mainly enriched in the 'p53 signaling pathway'. Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.

Stromal cell‑derived factor 2 (SDF2) is an endoplasmic reticulum chaperone protein crucial for protein folding. Its role in gliomas is poorly understood. The present study investigated SDF2 expression and function in glioma progression. Our data revealed that the expression of SDF2 was upregulated in glioma tissues. In glioma cell lines, SDF2 promoted cell proliferation and migration, whereas the knockdown of SDF2 (Ad‑shSDF2) induced cell death. Further investigations revealed that the copper chelator tetrathiomolybdate (TTM) could reverse the reduction in cell viability caused by Ad‑shSDF2. Upon SDF2 knockdown, the expression of ATP7A and ATP7B was decreased in glioma cells, whereas the expression of glucose‑regulated protein 78 (GRP78) was increased. Moreover, the proteasome inhibitor MG132 and the silencing of GRP78 effectively blocked the Ad‑shSDF2‑mediated decrease in ATP7A and ATP7B expression, as well as the accumulation of dihydrolipoamide S‑acetyltransferase in mitochondria. In vivo, SDF2 promoted subcutaneous tumor growth in nude mice, an effect that could be reversed by overexpression of GRP78. This reversal was accompanied by an increase in the intra‑tumoral copper ion concentration. In gliomas, SDF2 promotes tumor growth by inhibiting the GRP78‑mediated endoplasmic reticulum‑associated degradation pathway, thereby increasing the expression of ATP7A and ATP7B. This results in reduced intracellular accumulation of copper ions, facilitating tumor progression.

Phosducin-like 3 (PDCL3), a member of the photoreceptor family, is involved in angiogenesis and apoptosis. However, there is no pan-cancer analysis, and few studies have explored the effect of PDCL3 on tumor immune infiltration.

Public datasets were used to explore the diagnostic and prognostic value of PDCL3. The relationship between PDCL3 expression and immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) was investigated. Additionally, the therapeutic value of PDCL3 was explored. Finally, differences in PDCL3 expression across cell clusters were analyzed using single-cell datasets. In vitro cellular assays were performed to assess the impact of PDCL3 expression on the proliferative capacity, migratory potential, and invasive properties of non-small cell lung cancer (NSCLC) cells.

PDCL3 expression was upregulated in most tumors and correlated with poor outcomes, showing diagnostic and prognostic value. In addition, PDCL3 expression exhibited a positive correlation with infiltration of T helper 2 (Th2) cells and a negative correlation with infiltration of plasmacytoid dendritic cells (pDCs) across a variety of tumors. A relationship was also found between PDCL3 expression and TMB and MSI. Single-cell dataset analysis confirmed that PDCL3 expression was primarily in cancer cells and macrophages. In vitro functional analyses demonstrated that genetic silencing of PDCL3 significantly reduced proliferative rates, migratory activity, and invasive potential in pulmonary carcinoma cell models.

PDCL3 may contribute to cancer progression and is a potential candidate biomarker for pan-cancer diagnosis and prognosis. These findings suggest that targeting PDCL3 may provide a valuable strategy for cancer immunotherapy.

Retinoblastoma (RB) is the most common malignant eye tumor in children. Cytotoxic drugs like melphalam often cause significant side effects and acquired resistance in RB treatment. Here, the impact of Paraneoplastic Ma1 (PNMA1) on RB progression and chemotherapy resistance was investigated. A series of bioinformatics methods were used for differential expression genes and drug resistance genes screening. Western blot was performed for the detection of genes expression. CCK-8 and EdU staining were assessed for cell viability. Clone formation and TUNEL staining were examined for cell viability and apoptosis. Wound healing and transwell assays were analyzed for the cell migrated and invasive abilities. Immunofluorescence was observed for γ-H2AX expression. Colorimetric PARP/Apoptosis Assay was used for PARP activity. PNMA1 was upregulated in RB tumor tissues, and high expression of PNMA1 promotes RB cells' chemoresistance to melphalam, while downregulation of PNMA1 reversed chemoresistance in resistant cells. Furthermore, the mechanism by which PNMA1 mediated chemoresistance to melphalam, discovered that PNMA1 might facilitate melphalam resistance through the c-myc-mediated DNA damage repair pathway. PNMA1 functions as a tumor-promoting factor in retinoblastoma and may regulate melphalam resistance through the upregulation of the c-myc gene and the involvement in DNA damage repair.