Backgrounds: Cyclin-dependent kinase 7 (CDK7) plays key roles in transcription and cell cycle regulation, and its inhibition has been proposed as a potential therapeutic strategy for hepatocellular carcinoma (HCC). The primary research objective of this study is to identify and validate CDK7-associated prognostic genes in HCC using bioinformatics approaches, construct a reliable prognostic risk model, and explore the functional role of CDK7 in HCC progression through in vitro and in vivo experiments, with a specific focus on its association with RelA/p65 phosphorylation, so as to provide evidence supporting CDK7 as a potential prognostic biomarker and therapeutic target for HCC. Methods: Two independent HCC cohorts from The Cancer Genome Atlas (TCGA)-HCC and the Gene Expression Omnibus (dataset GSE14520) were analyzed. Patients were stratified by CDK7 expression. Differentially expressed genes were identified in both CDK7-based and tumor-versus-normal comparisons, and the intersection of these genes was analyzed. Univariate Cox regression and machine learning were used to screen prognostic genes and construct a risk model. The model's predictive utility was assessed using Kaplan-Meier and receiver operating characteristic (ROC) analyses. Mutation landscapes were compared between risk groups. The functional association of CDK7 was validated through in vitro and in vivo experiments. Results: Eight prognostic genes (CHGA, SH2D5, ACTBP12, SOX2, AGR2, ISM2, KRT12, and BRDT) were screened from 98 intersecting genes via univariate Cox regression and least absolute shrinkage and selection operator regression analyses to construct a risk model. In the TCGA-HCC (374 HCC samples and 50 control samples) and GSE14520 cohorts (222 HCC samples and 212 control samples), patients in the high-risk group had significantly worse overall survival than those in the low-risk group (Hazard Ratio [HR] = 0.003-0.036, 95% Confidence Interval [CI] = 1.01-4.28, p < 0.05). The predictive accuracy of the model was moderate, with the areas under the ROC curves (AUCs) for 1-, 3-, and 5-year survival exceeding 0.6 (specifically, 0.69 for 3-year survival). In vitro and in vivo experiments demonstrated that CDK7 expression is associated with HCC proliferation, migration, invasion, and tumor growth, and this association might be related to RelA/p65 phosphorylation. Conclusions: This study identified a novel eight-gene prognostic signature linked to CDK7 in HCC and provided experimental evidence that CDK7 promotes tumor aggressiveness. These findings suggest the potential of CDK7 as a prognostic biomarker and therapeutic target for HCC, though further validation of its clinical utility is needed.

Uncoupling protein 2 (UCP2) has been extensively studied as a metabolic regulator in glioma; however, its relationship with the tumour immune microenvironment and the cellular source of its expression within the glioma tumour microenvironment (TME) remains poorly understood. This study aimed to characterise UCP2 expression at single-cell resolution and evaluate its immunological significance in glioma.

This study employed an integrative multi-omics approach incorporating bulk transcriptomics, scRNA-seq (GSE70630, GSE84465, and GSE89567; n = 13,216 cells), immune deconvolution, immunohistochemistry (n = 96 glioma patients), and immunofluorescence co-staining (n = 6).

Pan-cancer analysis confirmed UCP2 overexpression in glioma. Single-cell analysis revealed UCP2 expression within the TME is predominantly enriched in macrophage/microglial populations rather than tumour cells, reframing UCP2 as a tumour-associated macrophage (TAM)-intrinsic regulator. In the TCGA cohort (n = 670), UCP2-high tumours exhibited an immunosuppressive landscape enriched with M2 macrophages and regulatory T cells, with elevated ESTIMATE scores. UCP2 correlated strongly with HAVCR2/TIM-3 (ρ = 0.847) and lactate metabolism genes, supporting a UCP2-lactate-TAM polarisation axis. TIDE analysis predicted that UCP2-high tumours may be associated with immunotherapy resistance. Multivariate Cox regression confirmed UCP2 as an independent prognostic factor (HR = 1.294, 95% CI: 1.116-1.502, p = 6.66 × 10^-4). UCP2 protein expression negatively correlated with Ki67 (ρ = -0.446, p = 5.23 × 10^-6), and immunofluorescence co-staining (n = 6) confirmed co-localisation with CD68-positive TAMs.

UCP2 functions as a TAM-intrinsic immune regulator and candidate biomarker for immunosuppressive TME characterisation and immunotherapy response stratification in glioma.

Myeloid sarcoma (MS) is a rare extramedullary tumor of immature myeloid cells. Intracranial MS occurring as an extramedullary relapse without concurrent systemic acute myeloid leukemia (AML), is exceptionally rare and poses a considerable diagnostic challenge due to its non-specific clinical and radiological features, often mimicking more common intracranial neoplasms like meningioma.

We report a case of isolated intracranial MS in a 61-year-old female with a prior history of FLT3-ITD mutated AML (M2), who had been in sustained complete hematologic remission for four years. She presented with a two-week history of diminished responsiveness and apathy. Cranial MRI revealed a well-defined, homogenously enhancing left frontal mass with a dural tail sign and significant peritumoral edema, initially suggestive of a meningioma. However, diffusion-weighted imaging (DWI) demonstrated restricted diffusion. The tumor was resected. Histopathological examination revealed diffuse sheets of immature myeloid cells. Immunohistochemistry was positive for CD117, CD34, and CD68, with weak MPO expression, confirming the diagnosis of MS. Post-operatively, the patient was referred for systemic chemotherapy.

This case illustrates that intracranial MS can be a form of extramedullary relapse in AML patients even during long-term remission and can closely mimic a meningioma radiologically. Key diagnostic clues include a prior history of AML and radiographic features such as restricted diffusion on DWI and prominent peritumoral edema. However, these findings are non-specific, and a definitive diagnosis relies on histopathological and immunohistochemical analysis. The management of MS should be based on systemic AML therapy principles rather than surgery alone. This report highlights the necessity of considering MS in the differential diagnosis of new intracranial masses in patients with a history of AML to ensure timely and appropriate treatment.

B-cell malignancies comprise a biologically diverse group of neoplasms, with only rare reports describing the co-occurrence of two distinct lymphoid entities. While concurrent presentation of mature B-cell neoplasms has been documented, the simultaneous occurrence of B-cell acute lymphoblastic leukemia (B-ALL) and plasma cell neoplasm (PCN) has previously been reported rarely. Such cases may provide insight into the clonal architecture and evolutionary pathways underlying lymphoid malignancies.

We report a 76-year-old man presenting with cytopenias and leukocytosis, in whom initial bone marrow evaluation and immunophenotyping established a diagnosis of B-ALL with a pre-B phenotype. At the time of diagnosis, flow cytometry also identified a distinct population of aberrant plasma cells, raising the possibility of a concurrent plasma cell neoplasm. Follow-up bone marrow analysis confirmed the coexistence of two immunophenotypically and morphologically distinct malignant populations: immature lymphoblasts consistent with B-ALL and clonal plasma cells. Initial ALL-directed therapy induced remission of both components. However, subsequent disease evolution demonstrated a clear phenotypic shift, with relapse characterized by expansion of a plasmablastic/plasma cell population consistent with PCN, while the B-ALL component remained undetectable by minimal residual disease assessment. Treatment was therefore redirected toward a myeloma-based regimen, which was limited by toxicity and failed to achieve disease control. Genomic analysis supported the presence of two clonally related but distinct malignancies.

These findings support a model of early clonal divergence from a common progenitor rather than independent malignancies or linear differentiation. This case highlights the complexity of clonal evolution in B-cell malignancies and underscores the importance of integrated genomic and immunophenotypic analysis in understanding disease biology.

Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), is a common endocrine and metabolic disorder in reproductive-age women, characterized by marked clinical and biological heterogeneity. Accumulating evidence suggests that gut microbiota dysbiosis is associated with metabolic disturbances, hormonal imbalance, and ovarian dysfunction in PMOS. However, the pathways linking gut microbiota alterations to PMOS pathogenesis remain incompletely understood, and most evidence remains associative. This review aims to summarize current evidence regarding interactions between gut microbiota and PMOS, clarify the roles of key microbiota-derived metabolites, and evaluate the potential and limitations of gut microbiota-targeted interventions. A major novelty is the proposal of an integrated gut-metabolism-endocrine-ovary axis incorporating phenotypic heterogeneity, methodological variability, and evidence grading across clinical and preclinical studies. A narrative review with a systematic literature search was conducted. PubMed, Web of Science, Embase, and CNKI were searched from inception to March 2026 using terms related to PMOS, gut microbiota, microbial metabolites, and microbiota-targeted interventions. Eligible studies included human observational or interventional studies, animal experiments exploring microbiota-PMOS mechanisms, and peer-reviewed full-text articles in English or Chinese. Case reports, letters, conference abstracts, non-English publications, and irrelevant studies were excluded. Duplicate records were removed. Two authors independently screened records and resolved disagreements by consensus. No meta-analysis was performed, and clinical registration was not applicable. Gut microbiota dysbiosis may contribute to PMOS through chronic low-grade inflammation, insulin resistance, and hyperandrogenism. Microbiota-derived metabolites link intestinal dysbiosis with metabolic and endocrine dysfunction. Bile acids and short-chain fatty acids exert regulatory effects, whereas amino acid disorders and LPS-mediated endotoxemia amplify metabolic and inflammatory abnormalities. Considerable heterogeneity exists across studies regarding obesity, insulin resistance, hyperandrogenism, diet, ethnicity, region, and methodology. Microbiota-targeted interventions show potential, although evidence quality varies and most findings remain associative. Gut microbiota dysbiosis is a critical regulatory node within the integrated gut-metabolism-endocrine-ovary axis in PMOS. This review highlights phenotypic stratification, evidence hierarchy, and clinical translation potential. Although microbiota-targeted strategies may serve as adjunctive therapies, their causal roles and long-term efficacy require confirmation in well-designed longitudinal and randomized controlled trials.

Cervical cancer (CC) remains one of the most prevalent malignancies in the female reproductive system. Methionine metabolism (MM) plays a pivotal role in various biological processes and has been implicated in cancer progression. However, its mechanisms in CC remain unclear.

Transcriptomic data from 305 patients in The Cancer Genome Atlas (TCGA) (training cohort) and 299 patients from the Gene Expression Omnibus (GEO) (GSE44001) (external validation cohort) were analyzed for differentially expressed MM-related genes (MM-RGs). Prognostic MM-RGs were identified using Cox regression, proportional hazards testing, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. A risk model was constructed and validated. Functional enrichment (Gene Set Enrichment Analysis/Gene Set Variation Analysis (GSEA/GSVA)), in-silico immune infiltration (CIBERSORT) and drug sensitivity (oncoPredict) analyses were performed. Five genes were validated by Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on clinical samples.

Eight MM-RGs (MTHFD1, SMYD2, MSRB3, MTR, ENOPH1, DNMT3B, SLC38A7, PEMT) were identified as prognostic genes. A robust risk score model was developed, stratifying patients into high- and low-risk groups with significant differences in survival outcomes. Functional enrichment revealed pathways such as ECM-receptor interaction and focal adhesion. Immune analysis indicated altered infiltration of Tregs and mast cells. In-silico drug sensitivity analysis predicted 57 agents with significantly different IC50 values between the high- and low-risk groups (p < 0.05). Notably, agents such as Cediranib and BI-2536 exhibited markedly lower IC50 values in the high-risk cohort, suggesting their potential efficacy for advanced-stage treatment. qRT-PCR preliminarily indicated the overexpression of four genes in CC tissues within a small clinical cohort.

This study establishes a novel MM-based prognostic model for CC and based on in-silico predictions suggests potential therapeutic targets through comprehensive transcriptomic and experimental validation.

To assess the utility of p57 in differentiating histological subtypes of hydatidiform mole and its applicability in clinical practice.

A scoping review was conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. The article search was conducted in the PubMed, EMBASE, BVS, Cochrane, Web of Science, and Scopus databases. Studies published between 2015 and 2025 that evaluated the use of p57 in suspected cases of hydatidiform mole were included.

Nine studies met the inclusion criteria. Most demonstrated high specificity of p57 for CHM diagnosis and a significant reduction in diagnostic discordance compared to morphology alone. However, p57 does not distinguish PHM from non-molar abortions. In addition, rare cases of divergent p57 expression were reported, associated with genetic alterations that may require complementary evaluation using molecular techniques.

IHC for p57 is a widely accessible, low-cost, and effective tool in clinical practice, particularly useful in resource-limited settings. Its routine use, in association with morphology and molecular methods when available, contributes to more accurate diagnoses and safer clinical management of GTDs.

Anti-programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 antibodies are efficacious in various malignancies. The potential role of dual checkpoint inhibitors in many rare solid tumors is not established.

This study presents the results of ipilimumab-nivolumab in salivary gland neoplasm cohorts of the SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) trial.

DART is a prospective, open-label, multicenter (1016 US sites), multi-cohort phase II trial of ipilimumab (1 mg/kg intravenously (IV) every 6 weeks) plus nivolumab (240 mg IV every 2 weeks).

We performed a prospective, multicenter phase II clinical trial of ipilimumab (1 mg/kg IV every 6 weeks) plus nivolumab (240 mg IV every 2 weeks) in three salivary gland neoplasm cohorts: major and minor salivary gland and adenoid cystic cancers. Patients with adenoid cystic salivary gland tumors (N = 26) and other salivary gland neoplasms (N = 34) were evaluable. The most common site of origin was the parotid (31%, N = 8 adenoid cystic group; 68%, N = 23 remaining histologies).

In the adenoid cystic group, objective response rate (ORR), 4% (complete response (CR) 0%, N = 0; partial response (PR) 4%, N = 1); 6-month progression-free survival (PFS) and overall survival (OS), 32% (95% confidence interval (CI) 18%-57%) and 84% (95% CI 71%-100%), respectively. In the remaining histologic subtypes, the confirmed ORR was 9% (CR, 0%, N = 0; PR, 9%, N = 3); stable disease (SD) >6 months/PR/unconfirmed PR = 35%; 6-month PFS and OS, 34% (95% CI 21%-55%) and 88% (95% CI 78%-100%), respectively. The most common toxicities were fatigue (39%) and diarrhea (26%); diarrhea (8%) was the most common grade 3-4 immune-related adverse event.

In salivary gland tumors, combined ipilimumab plus nivolumab resulted in only a 4% ORR in adenoid cystic carcinoma and 9% in all other histologies combined, though the latter showed clinical benefit (included SD >6 months) in 35% of patients.Trial registration: ClinicalTrials.gov registry: NCT02834013.

Acute myeloid leukemia (AML) and related myeloid malignancies remain clinically challenging despite recent advances in molecular profiling and targeted therapy. Although recurrent oncogenic drivers have improved disease classification and informed therapeutic development, durable disease control remains limited by signaling plasticity and therapeutic resistance of heterogeneous malignant stem and progenitor populations. These limitations drive continued interest in signaling dependencies that investigate oncogenic inputs across genetically diverse myeloid disease states. The p90 ribosomal S6 kinase (RSK) family has emerged as one such candidate. Positioned as a downstream convergence of MAPK/ERK and PI3K/PDK-1 signaling, RSK regulates proliferation, survival, translational control, inflammatory signaling, and cellular stress adaptation, all processes directly relevant to malignant progression. Growing evidence supports aberrant RSK activation in AML, functional dependency in FLT3-mutant AML and myeloproliferative neoplasms/myelofibrosis, and increasing translational interest in selective pharmacologic inhibition. Early preclinical studies demonstrate anti-leukemic activity through both genetic and pharmacologic targeting, while emerging clinical development of RSK inhibitors in solid tumors supports therapeutic feasibility. Here, we review the biologic role of RSK signaling in myeloid malignancies and discuss the therapeutic opportunities and challenges associated with targeting this signaling axis.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare and aggressive neoplasm that is characterized by EWSR1 rearrangements. Most patients present with metastatic disease. There are no established treatment guidelines, and systemic therapy options remain poorly defined.

A woman in her late 30s presented initially with right upper quadrant pain and bloating. Endoscopic biopsy of a duodenal mass revealed a SOX10-positive malignant neoplasm. Molecular testing identified an EWSR1:CREB1 fusion, confirming GNET. Initial treatment with ipilimumab and nivolumab resulted in disease progression. Subsequent therapies included a selective interleukin-2 agonist clinical trial, nivolumab/relatlimab, and temozolomide, all associated with continued progression. Cabozantinib was initiated after further radiographic progression. Follow-up imaging demonstrated tumor regression, and the patient maintained stable disease for 15 months before mild progression.

Metastatic GNET has a poor prognosis and lacks standardized systemic therapy. This case demonstrates durable disease stabilization with cabozantinib after progression on immunotherapy and chemotherapy. Tyrosine kinase inhibition may represent a promising therapeutic strategy in GNET and warrants further investigation.