• Patient-derived organoids in functional precision oncology: from experimental models to clinical decision-making.
    2 weeks ago
    Despite major advances in high-throughput genomics, proteomics, and multimodal imaging, a substantial gap persists between molecular tumor characterization and clinically actionable therapeutic decision-making, partly due to the limitations of conventional preclinical models in capturing tumor heterogeneity and predicting patient-specific drug response. Patient-derived organoids (PDO) have emerged as a promising platform to bridge this gap by enabling functional interrogation of individual tumors in a physiologically relevant three-dimensional context. PDO retain the genomic, transcriptomic, and histopathological features of their parental tumors while supporting long-term expansion, biobanking, and high-throughput pharmacological testing. In this review, we provide a clinically oriented overview of PDO technology as a key tool in functional precision oncology, summarizing current methodologies for tissue processing, organoid derivation, and quality control. We examine applications across multiple cancer types, including drug screening, radiotherapy response modeling, immuno-oncology co-culture systems, and CRISPR-based functional genomics, highlighting their role in directly measuring therapeutic vulnerability. We also integrate tumor-specific evidence across major malignancies, including colorectal, pancreatic, and breast cancers, where PDO-based pharmacotyping shows strong concordance with clinical outcomes and is increasingly incorporated into prospective trials. Finally, we discuss the integration of PDO with emerging technologies, including organoid-on-chip systems, artificial intelligence-driven analytics, and hospital-integrated workflows, as a critical innovation layer that is redefining their clinical applicability. These integrative approaches move PDO beyond static ex vivo models toward dynamic, and decision-support systems, with the potential to substantially enhance predictive accuracy and real-time therapeutic stratification. Collectively, these advances position PDOs as a promising component in next-generation precision oncology, supporting a transition from static genomics-based stratification toward dynamic, functionally guided therapeutic decision-making.
    Cancer
    Care/Management
  • Diagnostic performance of serum vitamin D metabolites and 14 inorganic elements in early prediction of kidney neoplasm.
    2 weeks ago
    This study aimed to identify potential biomarkers by profiling serum vitamin D (VitD) metabolites and fourteen trace elements, with the goal of screening kidney neoplasm (KN) before symptom onset.

    The study included 57 renal cell carcinoma (RCC) patients, 43 patients with benign KN (BKN), and 50 healthy controls. Serum levels of VitD metabolites, including 25(OH)D2, 25(OH)D3, and C3-epi-25(OH)D3, were quantified using UPLC-MS/MS. The t-25(OH)D was calculated, and f-25(OH)D level was measured by ELISA. Serum concentrations of 14 inorganic elements, including calcium (Ca), magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), selenium (Se), manganese (Mn), cobalt (Co), silver (Ag), gallium (Ga), cesium (Cs), lead (Pb), cadmium (Cd), and arsenic (As), were determined by ICP-MS.

    RCC and BKN patients exhibited significantly lower serum levels of t-25(OH)D, 25(OH)D3, f-25(OH)D, Ca, Mg, Fe, Zn, and Ag compared to healthy controls, while C3-epi-25(OH)D3 levels were significantly elevated (P < 0.05). Additionally, RCC patients had significantly lower levels of Zn and Se, but higher levels of Ga, than BKN patients (P < 0.05). Correlation analysis revealed significant positive associations between Fe and Cs with t-25(OH)D, 25(OH)D3, C3-epi, and f-25(OH)D, as well as between Ca and t-25(OH)D and f-25(OH)D (P < 0.05). Logistic regression analysis identified f-25(OH)D (OR = 0.762, P < 0.040), Fe (OR = 0.943, P < 0.028), and Zn (OR = 0.945, P = 0.001) as protective factors against KN, while C3-epi-25(OH)D3 (OR = 84.974, P < 0.001) was a risk factor. Receiver operating characteristic (ROC) curve analysis showed that the combination of C3-epi, f-25(OH)D, and Zn (AUC = 0.895), or C3-epi, Fe, and Zn (AUC = 0.912), did not significantly differ from the four-marker combination of C3-epi, f-25(OH)D, Fe, and Zn (AUC = 0.924). All combined approaches outperformed individual or two-marker assays (all P < 0.05).

    KN patients exhibit altered VitD metabolites and trace element profiles, with low Zn and Se potentially promoting malignancy. Free-25(OH)D, Fe, and Zn serve as protective factors, while C3-epi predisposes to disease. Combining C3-epi with f-25(OH)D and Zn, or with Fe and Zn, provides strong diagnostic accuracy for KN.
    Cancer
    Care/Management
  • A case of well-differentiated papillary mesothelial tumor concomitant with primary gastric cancer: case report and literature review.
    2 weeks ago
    Well-differentiated papillary mesothelial tumor (WDPMT) is a rare neoplasm characterized by low malignant potential. Due to the absence of distinct clinical symptoms, WDPMT is frequently detected incidentally during surgical procedures.

    This report describes a patient diagnosed with primary gastric cancer (GC) and concomitant WDPMT. The lesion was identified during laparoscopic radical gastrectomy and subsequently confirmed via histopathological and immunohistochemical analysis. No recurrence or disease progression was observed during a two-year postoperative follow-up period.

    WDPMT remains a relatively rare disease. In addition to histopathological evaluation, immunohistochemistry and, where available, molecular genetic analysis contribute to diagnostic accuracy. However, conclusive evidence from large-scale studies are currently lacking. The overall prognosis of WDPMT is favorable, with surgical excision representing the standard therapeutic approach.
    Cancer
    Care/Management
  • Systemic inflammatory biomarkers (NLR, SII, PNI and FPR) combined with CEA for predicting advanced colorectal neoplasms: development and temporal validation of a machine learning model.
    2 weeks ago
    Chronic systemic inflammation is closely associated with the initiation and development of colorectal tumors. Biomarkers reflecting inflammatory status may help detect advanced colorectal neoplasms (ACRN), which include advanced adenoma and colorectal cancer. Nevertheless, the diagnostic ability of combined inflammatory and nutritional indicators for ACRN has not been fully clarified. This study evaluated whether several systemic inflammation markers-NLR, SII, PNI, and FPR-together with CEA, can improve the identification of ACRN.

    A retrospective analysis was conducted in individuals who received colonoscopy from December 2016 to December 2024. Eligible subjects were randomly assigned to a training set and an internal testing set. Patients enrolled between January 2025 and January 2026 were used as a temporal validation cohort. Correlation analysis together with restricted cubic spline (RCS) modeling was applied to assess the associations between inflammatory markers and ACRN risk. Machine learning approaches were then used to construct prediction models based on NLR, SII, PNI, FPR, and CEA. Model performance was assessed by discrimination ability, calibration, and clinical usefulness. An online calculator was also established to support individualized risk estimation.

    A total of 1330 individuals were analyzed, including 252(18.95%) cases diagnosed with ACRN. Higher values of NLR, SII, FPR, and CEA were linked to a greater probability of ACRN, while PNI showed a negative relationship. These indicators also displayed clear changes across different stages of disease. Among the evaluated machine learning approaches, the XGBoost model showed the strongest predictive ability. The AUCs reached 0.960 in the training set, 0.944 in the testing set, and 0.908 in the temporal validation cohort. In addition, a web-based calculator was built to support personalized risk assessment.

    Systemic inflammatory and nutritional biomarkers combined with CEA demonstrated robust predictive performance for identifying advanced colorectal neoplasms and may provide a convenient tool for early risk stratification in colorectal cancer screening.
    Cancer
    Care/Management
  • The role of OTUD1-mediated deubiquitination in disease pathogenesis: from molecular mechanisms to clinical translation.
    2 weeks ago
    OTUD1 is a deubiquitinase of the OTU family that participates in immune signaling, redox balance, and cell death through modulating substrate ubiquitination. Under physiological conditions, OTUD1 primarily exerts negative regulatory effects, restricting excessive activation of NF-κB inflammatory signaling and type I interferon responses, thereby maintaining immune and oxidative homeostasis. Under pathological conditions, its functional effects undergo tissue-dependent reprogramming: it is downregulated in most epithelial tumors and suppresses malignant progression, whereas it is upregulated in certain tumors and cardiovascular or metabolic diseases and promotes pathological remodeling. It exerts protective regulation in the nervous system and mucosal inflammation, yet drives hypertrophy and fibrosis in the cardiovascular system. Preclinical studies indicate that OTUD1 expression levels correlate with tumor stage, prognosis, and therapeutic sensitivity, suggesting potential as a biomarker for diagnostic subtyping and prognostic assessment. However, marked tissue functional heterogeneity, the discovery of non-enzymatic scaffold functions, and the lack of highly selective targeting probes constitute central bottlenecks for clinical translation. This review systematically summarizes the molecular characteristics, physiological functions, disease regulatory networks, and current clinical translational status of OTUD1, with the aim of clarifying the molecular basis of its functional duality and providing a theoretical foundation for optimizing precision diagnostic and therapeutic strategies targeting OTUD1.
    Cancer
    Cardiovascular diseases
    Care/Management
    Policy
  • LMP1 Activates the Wnt/β-Catenin Signaling Pathway and Promotes Nasopharyngeal Carcinoma Progression Through Its Interaction With DVL2.
    2 weeks ago
    Nasopharyngeal carcinoma (NPC) is a type of cancer that is prevalent in southern China. In the development of NPC, the oncogenic protein LMP1, which is encoded by EBV, plays a very important role. The Wnt pathway is abnormally activated in many types of malignant tumors. The interaction between AXIN and DVL2 is pivotal for the breakdown of the β-catenin destruction complex and Wnt/β-catenin pathway activation. However, the molecular mechanisms underlying this process in NPC are not well understood. In this study, we identified the transmembrane protein LMP1 as an interacting partner of DVL2, which positively regulates the Wnt/β-catenin pathway by inhibiting the AXIN-DVL2 interaction. LMP1 overexpression enhanced NPC cell growth, metastasis, and stemness, whereas LMP1 knockdown suppressed these abilities. Our findings reveal new oncogenic roles for LMP1 in NPC progression.
    Cancer
    Care/Management
  • Cancer-related mortality among individuals with schizophrenia: systematic review and meta-analysis of cohort studies.
    2 weeks ago
    Individuals with schizophrenia have shown distinct cancer incidence patterns.

    We aimed to assess whether their cancer-related mortality differs from the general population overall, by gender and by specific cancer types.

    We systematically searched Scopus, Web of Science, PsycINFO, PubMed and Embase, up to December 2025. Each record was independently screened by two reviewers, and data were independently extracted by two investigators. Two authors assessed the quality of the included articles with the Newcastle-Ottawa Scale. Analyses were conducted using Stata version 16; between-study heterogeneity was evaluated with Cochran's Q-statistic and the I2-statistic, and potential sources of heterogeneity were further examined through exploratory meta-regression.

    Meta-analysis of cohort studies showed that individuals with schizophrenia had a 55% higher risk of cancer-related death than the general population (standardised mortality ratio (SMR) 1.55; 95% CI 1.16-2.07). In gender-stratified analyses, SMRs for all cancers combined were 1.37 (95% CI 1.01-1.87) in men and 1.43 (95% CI 1.15-1.79) in women. Site-specific SMRs were 1.77 (95% CI 1.17-2.68) for breast, 2.40 (95% CI 2.35-2.45) for respiratory, 1.54 (95% CI 1.35-1.76) for gastrointestinal, 2.32 (95% CI 0.72-7.45) for haematologic, 4.43 (95% CI 0.71-27.62) for skin and soft tissue, 3.03 (95% CI 1.96-4.69) for urogenital and 1.01 (95% CI: 0.36-2.83) for other cancers, although precision varied considerably across cancer sites.

    Schizophrenia was associated with substantially elevated cancer-related mortality compared with the general population. These findings underscore the need for earlier cancer detection and guideline-concordant, integrated physical and mental healthcare for this high-risk group.
    Cancer
    Mental Health
    Care/Management
  • A Novel Aerogel Delivery System Reduces Drug Resistance for Non-Small Cell Lung Cancer Combination Therapy.
    2 weeks ago
    Lung cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) representing the predominant subtype. Despite advances with molecularly targeted therapies, the prognosis remains poor because of drug resistance. Combination therapy with docetaxel and gefitinib offers synergistic potential but is limited by systemic side effects from nonspecific uptake. Here, we developed an inhalable aerogel-based nanocarrier for the efficient codelivery of docetaxel and gefitinib, designed to enhance lung tumor accumulation while reducing systemic toxicity. Inhalation administration resulted in significant drug enrichment in tumors and achieved a tumor inhibition rate of 55.4% ± 3.6% in an NSCLC xenograft model, with reduced resistance compared with monotherapy. Mechanistically, the aerogel synergistically suppressed angiogenesis and promoted apoptosis. These findings underscore the potential of inhalable aerogels as a promising strategy for effective NSCLC therapy and clinical translation.
    Cancer
    Chronic respiratory disease
    Care/Management
  • RIOK2 Promotes Clear Cell Renal Cell Carcinoma Progression Through Cell Cycle Regulation.
    2 weeks ago
    Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer and is frequently associated with poor clinical outcomes. Ribosome biogenesis, which is upregulated in many malignancies, plays a key role in tumor proliferation. Right open reading frame kinase 2 (RIOK2) is an atypical kinase essential for 40S ribosomal subunit maturation, but its role in ccRCC remains unexplored. We investigated the clinical and biological significance of RIOK2 in ccRCC. Immunohistochemical analysis of 166 ccRCC specimens revealed that high RIOK2 expression was significantly associated with advanced pathological stage, higher tumor grade, and shorter cancer-specific and progression-free survival. Public datasets confirmed the elevated RIOK2 mRNA expression in ccRCC, and its association with poor prognosis. Functional studies demonstrated that RIOK2 knockdown suppressed the proliferation, invasion, and migration of ccRCC cells. RNA sequencing, followed by gene set enrichment analysis, revealed that RIOK2 knockdown led to the downregulation of cell cycle-related pathways, including E2F targets. Analyses of public datasets further highlighted suppression of the G2/M checkpoint. Flow cytometry revealed G1 cell cycle arrest accompanied by reduced CDK2 protein expression in RIOK2-knockdown cells. Furthermore, the small-molecule RIOK2 inhibitor, NSC139021, suppressed ccRCC cell proliferation in a dose-dependent manner, with reduced efficiency in RIOK2-knockdown cells. Collectively, these findings identify RIOK2 as a clinically relevant factor associated with aggressive disease behavior and cell-cycle regulation in ccRCC.
    Cancer
    Care/Management
    Policy
  • Optimizing Management of Leydig Cell Tumors: 27-Year Experience of Avoiding Frozen Sections Guided by Expert Radiological Assessment.
    2 weeks ago
    Leydig cell tumors (LCTs) are rare, usually benign testicular tumors for which frozen section examination is commonly recommended during testis-sparing surgery (TSS). We report a 27-year single-center experience, emphasizing the role of imaging for conservative surgery decision-making. It shows our experience using expert radiology assessment to direct TSS without frozen section examination.

    In this retrospective observational study, we reviewed our institutional database of testicular tumors treated between 1998 and 2025. Patients with histologically confirmed LCTs were included. Clinical presentation, hormonal profile, imaging characteristics, surgery type, and intraoperative frozen section use were analyzed.

    Among 481 testicular tumors, 68 (14.14%) were LCTs. Within the histologically confirmed LCTs cohort, preoperative expert radiology assessment achieved 97% (66/68) concordance with the final pathology. Partial orchiectomy was performed in 62 cases (91.18%), total orchiectomy in 6 (8.82%). Median age was 36 years. Median follow-up was 75 months. No malignant LCTs were observed. All patients remained in complete remission. The most common reasons for consultation were infertility (n=41, 60.29%) where systematic ultrasound screening discovered the lesion, gynecomastia (n=4, 5.88%), Klinefelter syndrome work-up (n=4, 5.88%; 2 additional cases identified within the infertility group, total n=6) and palpable nodule (n=4, 5.88%). Median ultrasound tumor size was 7 mm (range: 2 to 32 mm).

    Radiological characteristics effectively differentiated LCTs, suggesting that direct TSS without frozen section examination might be feasible when expert radiological evaluation is available. Our findings reflect radiology-pathology concordance within histologically confirmed LCTs rather than diagnostic accuracy in an unselected population. This approach optimizes surgical workflow, preserves endocrine function and fertility. No recurrence was observed. Frozen section examination should be maintained where expert radiology consultation is unavailable or diagnostic uncertainty exists. Prospective validation is required before omitting frozen section examination outside expert centers.
    Cancer
    Care/Management