Breast cancer accounts for 14% of all cancer-related deaths among women. Women aged 50-69 years are offered biennial mammography, which reduces breast cancer-specific mortality. Simulations suggest that risk-stratified screening detects more early-stage cancers while lowering the number of unnecessary recalls, assessments and biopsies in low-risk women. This trial will investigate whether multifactorial risk-stratified screening, including polygenic score, is feasible, acceptable, cost-efficient and safe.

The increasing availability of large-scale omics data calls for robust analytical frameworks capable of handling complex gene expression datasets while offering interpretable results. Recent advances in artificial intelligence have enabled the identification of aberrant molecular patterns distinguishing disease states from healthy controls. Coupled with improvements in model interpretability, these tools now support the identification of genes potentially driving disease phenotypes. However, current approaches to gene anomaly detection often remain limited to single datasets and lack accessible graphical interfaces. We introduce E-ABIN, a general-purpose, explainable framework for anomaly detection in biological networks. E-ABIN combines classical machine learning and graph-based deep learning techniques within a unified, user-friendly platform, enabling the detection and interpretation of anomalies from gene expression or methylation-derived networks. By integrating algorithms such as support vector machines, random forests, graph autoencoders, and graph adversarial attributed networks, E-ABIN ensures high predictive accuracy while maintaining interpretability. We demonstrate the utility of E-ABIN through case studies of bladder cancer and celiac disease, where it effectively uncovers biologically relevant anomalies and offers insights into disease mechanisms. E-ABIN is freely available on the Zenodo platform at https://doi.org/10.5281/zenodo.17062501.

Thyroid cancer, the most prevalent endocrine malignancy, poses significant therapeutic challenges due to its heterogeneous biological behavior. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine, is implicated in tumor progression and senescence regulation in various cancers. However, its role in thyroid cancer, particularly its interaction with the p53 signaling pathway, remains poorly understood. This study aimed to investigate the functional contribution of GDF15 to thyroid cancer progression and its regulatory mechanism in cancer cell senescence.

Alternative splicing is a crucial mechanism of gene regulation that can be dysregulated in cancer. In pituitary neuroendocrine tumors (PitNETs), alteration in the serine/arginine-rich splicing factors (SRSFs) has been reported. SRSFs phosphorylation and activation is mediated by serine-arginine protein kinase 1 (SRPK1). SRPK1 is considered a proto-oncogene and its inhibition by small molecule inhibitors SRPIN340 and SPHINX31 have shown antitumoral effects via the SRPK1-SRSF1-VEGF pathway modulation in different cancer types. No previous studies have evaluated SRPK1 inhibitors in pituitary tumors. The present work explores the antitumoral effects of SRPIN340 and SPHINX31 in rat and human GH-secreting pituitary tumoral cells. First, immunoblot results showed a reduction of SRSFs phosphorylation induced by both compounds, demonstrating the efficacy of these molecules in inhibiting SRPK1 activity. SRPIN340 reduced GH4C1 cell proliferation (-31.7 (33.6)%, p <0.05 vs control cells at 1µM), cell viability (-16.4 (27.9)%, p<0.05 vs control cells at 1µM), cell migration (-65.0 (46.3)%, p<0.001 vs control cells at 10µM) and induced cell apoptosis (+40.5 (26.6)%, p<0.05 vs control cells at 10µM). Moreover, SRPIN340 significantly decreased both transcript (-56.3 (38.6)%, p<0.01 vs control cells) and protein levels (-33.5 (3.4)%, p<0.05 vs control cells) of the pro-survival VEGF164a isoform. Similar results have been obtained with SPHINX31. Interestingly, cells incubation with the recombinant VEGF164a protein impaired the decrease of cell migration and cell viability mediated by both SRPK1 inhibitors. As for GH-secreting primary cultures from GH-PitNETs, SRPIN340 incubation resulted in reduced VEGF165a expression (-50.6% vs control cells) and GH secretion (-14.45 (8.17)%, p < 0.05 vs control cells). In conclusion, SRPK1 inhibition may represent a novel approach to exert antitumoral effects in somatotroph tumoral cells via SRPK1-SRSF1-VEGF pathway regulation.

This study explores the genetic basis of membranous nephropathy (MN) in gastric adenocarcinoma (GC) through bioinformatics and machine learning analyses.

Neoantigens have emerged as promising targets for personalized cancer immunotherapy due to their tumor-specific immunogenicity. However, current neoantigen prediction methods relying on combined DNA/RNA sequencing are costly and time-consuming, limiting clinical applicability. This study aimed to establish a streamlined neoantigen identification pipeline using RNA sequencing alone, evaluating its efficacy in breast and lung cancer models.

Small cell carcinoma of the esophagus (SCCE) is a rare and highly aggressive malignancy with limited therapeutic options and poor prognosis. The paucity of clinical specimens and lack of established experimental models have hindered a comprehensive understanding of its cellular heterogeneity and tumor microenvironment.

Mesothelin (MSLN) is a cell-surface glycoprotein overexpressed in the majority of pancreatic ductal adenocarcinoma (PDAC) cases and represents a promising immunotherapeutic target. Despite studies and clinical trials investigating MSLN-targeted immunotherapies, its biological role in PDAC carcinogenesis and influence on the tumor microenvironment remain poorly characterized. This study aims to investigate MSLN expression patterns in PDAC and assess their relationship to clinical outcomes and the immune microenvironment.

Circular RNAs (circRNAs) have been reported to be important in the development and progression of breast cancer. Nevertheless, the biological functions and mechanisms underlying the action of circRNAs in triple-negative breast cancer (TNBC) remain poorly understood. The present study aimed to explore the role of hsa_circ_0001910 (also termed circWWC3) interacting with vimentin in regulating the secretion of Colony Stimulating Factor 2 (CSF2) and its effects on the malignant biological behavior of triple-negative breast cancer as well as the cytotoxic activity of NK cells.

Glioma, the most prevalent primary brain tumor, exhibits dysregulated ribosome biogenesis closely linked to malignant behavior. However, the role of ribosome biogenesis in glioma and prognosis remains incompletely understood. This study aimed to construct a molecular signature based on ribosome biogenesis-related genes to predict patient survival and therapeutic response in glioma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and is most often caused by cumulative UV exposure. However, cSCC may also arise independently of UV exposure, on sites of sustained skin damage like chronic ulcers, scars, Recessive Dystrophic Epidermolysis Bullosa (RDEB), and inflammatory skin diseases such as hidradenitis suppurativa (HS). Little is known about non-UV-induced skin carcinomas. We aimed to describe the clinical, pathological, and genetic features, of non-UV-induced cSCC. We collected clinical and pathologic data corresponding to 31 patients with non-UV-induced cSCC, including 5 cSCC on HS, 4 on chronic leg ulcers and 8 on RDEB. DNA was extracted from FFPE samples and analysed using a NGS assay targeting 523 cancer genes. A comparison was performed with published genetic data obtained in non-UV-induced and UV-induced cSCC. We found that the Tumour Mutational Burden (TMB) of non-UV-induced cSCC was 6-times lower than the published TMB of UV-induced cSCC. The predominant mutational signature was a clock-wise signature. By comparing the frequency of driver mutations, we found TP53 and NOTCH1 to be significantly less frequently mutated than in UV-mutated cSCC. Interestingly, KMT2B (a histone methyl transferase) was mutated in 11/31 non-UV-induced cSCC and this proportion was significantly higher than in UV-mutated cSCC. These mutations were high impact loss-of-function mutations. We found that knocking down KMT2B expression using siRNA did not affect cell proliferation of SCC-13 and A-431 cell lines, however, it significantly increased cell migration in vitro. Taken together, this study provides a comprehensive description of non-UV-induced cSCC and identifies that KMT2B is mutated and involved in non-UV-induced cSCC carcinogenesis. © 2025 The Pathological Society of Great Britain and Ireland.

Multiple myeloma (MM) is a malignant neoplasm of plasma cells leading to bone destruction and marrow failure. Prognosis and management of MM rely on cytogenetic determination of copy number alterations (CNAs). Nevertheless, karyotype analysis difficult due to the presence of few plasma cells and their low proliferative activity. A shallow whole-genome sequencing (sWGS) technology named LeukoPrint was used to detect genome-wide CNAs in MM patients (n = 128), which can cover the entire genome without involving cell culture. Compared with karyotyping and fluorescent in situ hybridization (FISH), LeukoPrint demonstrated a significantly higher detection rate of copy number alterations (CNAs), increasing from 8.0% (karyotyping) and 44.2% (FISH) to 75.0% (n = 96), provided new CNA information and redefined the prognostic stratification in 20.3% of patients according to mSMART guidelines. Hyperdiploidy was the most common CNA feature (39.6%) in this cohort. A high concordance of 90.7% was observed in CNA between matched bone marrow and peripheral blood samples. LeukoPrint can be regarded as an automated, convenient and cost-effective approach to describe genomic CNA profiles. With the advantage of detecting CNAs of short segments and incorporating routine diagnostic methods, LeukoPrint can add value to conventional karyotyping with improved prognostic stratification.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.

Prostate cancer (PCa) is one of the prevalent cancers in men. Although deubiquitinating enzymes are implicated in tumorigenesis and progression, the specific role of ubiquitin specific peptidase 21 (USP21) in PCa remains unclear. This study provides the first comprehensive analysis of USP21 as a key oncogene driving PCa progression.

Hepatocellular carcinoma (HCC) is one of the most common aggressive malignant tumors worldwide with poor clinical outcomes and high mortality rates, highlighting the pressing need to identify reliable biomarkers. Nucleolar protein 11 (NOL11), as an essential element for ribosomal biosynthesis, has been implicated in the development and progression of various diseases. However, the potential role of NOL11 in HCC remains elusive.

Phosphodiesterase-5 (PDE5) inhibitors have been shown to have potential as an adjuvant therapy for cancer. Tadalafil is a potent and selective PDE5 inhibitor that has been shown to inhibit the aggregation of myeloid-derived suppressor cells (MDSC) within tumors. Given the pivotal role of STAT3 signaling in mediating MDSC immunosuppression, we investigated the impact of tadalafil on MDSC differentiation and inhibitory function. Our findings indicate that tadalafil significantly attenuates in situ breast tumor growth and metastasis while impairing the capacity of MDSCs to suppress T-cell proliferation, concomitant with reduced STAT3 phosphorylation. Transcriptomic analysis revealed that tadalafil modulates MDSC metabolism, upregulates NAD+ nucleotidase activity, and disrupts chemotaxis-related transcriptional programs, including downregulation of key chemokine receptors. Consistent with these observations, in vitro migration assays confirmed tadalafil-mediated inhibition of MDSC chemotaxis toward tumor cells. Furthermore, tadalafil markedly enhanced nuclear PARP1 expression, which exhibits a negative regulatory relationship with STAT3. Collectively, these data demonstrate that tadalafil exerts systemic and local immunomodulatory effects on MDSCs during tumor infiltration, primarily through PARP1-STAT3 axis regulation. These insights underscore the therapeutic potential of tadalafil in reprogramming MDSC-mediated immunosuppression in cancer.

Meningioma is a common central nervous system tumor that poses serious health hazards and increases with age. However, the role of immune cells in meningioma remains incompletely understood.

Single nucleotide polymorphisms (SNPs) in FSHR were reported to increase PCOS susceptibility. The present study was conducted to analyse the association of FSHR polymorphisms (rs1394205, rs11692782, and rs2349415) with PCOS in Punjab, India.

Long non-coding RNAs (lncRNAs) play crucial role in tumor development and are being explored as potential therapeutic targets in lung cancer. Both SOX2OT and SOX2 are consistently overexpressed in lung cancer, suggesting that SOX2OT may play a significant role in its development. This study examines how knocking down SOX2OT affects the expression of specific lncRNAs (LINC00982, LINC00668, SNHG7), the gene P16, and key cell cycle-regulating proteins (HSP90AA1, EP300, YES1) in lung cancer cells. Silencing of SOX2OT in A549 and Calu-3 cells led to a marked reduction in its expression. This downregulation was accompanied by decreased levels of SNHG7 and LINC00668, while LINC00982 and P16 transcripts were strongly induced. At the protein level, EP300, HSP90AA1, and YES1 were substantially reduced, whereas P16 was notably elevated. Functionally, suppression of SOX2OT impaired cell viability and significantly limited migratory capacity. In parallel, apoptosis assays demonstrated a pronounced increase in apoptotic cell populations following SOX2OT knockdown. SOX2OT regulates specific lncRNAs and proteins involved in lung cancer survival and migration. Silencing SOX2OT significantly reduces viability, migration, and survival of lung cancer cells, suggesting its potential as a therapeutic target. Further in vivo validation and rescue experiments are needed to confirm these mechanisms.