Bacterial flora is present in various parts of the human body, and bacterial 16S rRNA genes have been detected in the bloodstream. Distinct blood microbiomes have been identified in various diseases, including cancer, and are thought to play a role in disease pathogenesis. In this study, we conducted a 16S rRNA metagenomic analysis of serum extracellular vesicles from 89 patients with gastric cancer (GC) and 25 healthy donors. We identified lower levels of Bacteroidetes and Actinobacteria and higher levels of Firmicutes in patients with GC than in healthy donors. By integrating this characteristic bacterial DNA profile, we developed a BAF index, defined as the ratio of Bacteroidetes and Actinobacteria to Firmicutes, which exhibited high sensitivity for detecting GC in both the discovery and validation cohorts, suggesting its potential utility as a screening tool. A high BAF index was significantly associated with an advanced tumor stage and poor prognosis. Moreover, a high BAF index was linked to an immunosuppressive tumor microenvironment, which may contribute to the unfavorable outcomes observed in these patients. These findings indicate that circulating bacterial signatures may serve as promising biomarkers for GC.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition that has been suggested to increase cancer risk, but the incidence and types of associated malignancies remain unclear. This study aimed to evaluate the cancer risk in patients with IgG4-RD using a nationwide population-based cohort. We identified 2,150 patients newly diagnosed with IgG4-RD between January 2012 and December 2020 from the Korean National Health Insurance Service database. Patients were followed until the occurrence of cancer, death, or December 31, 2021. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence in IgG4-RD patients with that in the general population. Subgroup analyses were conducted based on sex, age at diagnosis, follow-up duration, and use of immunosuppressive agents. Patients with IgG4-RD had a significantly increased risk of overall cancer (SIR 4.12, 95% CI 3.48-4.85), including solid tumors (SIR 3.33, 95% CI 2.74-4.02) and hematologic malignancies (SIR 15.31, 95% CI 10.17-22.13). Among solid tumors, the highest risks were observed for pancreatic cancer (SIR 14.54, 95% CI 8.31-23.62), central nervous system cancer, and biliary tract cancer. Myelodysplastic syndrome and non-Hodgkin lymphoma were the most frequent hematologic cancers. Cancer risk was higher in female patients. The risk peaked within the first year after IgG4-RD diagnosis (SIR 7.13, 95% CI 5.65-8.89). Patients with IgG4-RD have a significantly elevated risk of developing cancer, particularly myelodysplastic syndrome, non-Hodgkin lymphoma, pancreatic cancer, and biliary tract cancer. Close surveillance for malignancy is warranted, especially during the first year after diagnosis.

The study aimed to investigate the independent effects of serum branched-chain and aromatic amino acid levels on hepatocellular carcinoma (HCC) development. This multicenter retrospective study included patients with chronic liver disease (CLD) from two institutions in Japan. Amino acid imbalance was assessed using BCAA and tyrosine levels. Factors associated with the development of HCC and mortality were assessed using Fine-Gray competing risk and Cox proportional hazards regression models, respectively. Among 563 patients, the median age was 67 years, and 51% were male. During a median follow-up period of 3.5 years, 14% (n = 80) of the patients developed HCC and 23% (n = 130) died. Given mortality as a competing risk, multivariable analysis showed that the serum tyrosine level (sub-distribution hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00-1.02) was an independent risk factor for the development of HCC. Similarly, using the development of HCC as a time-dependent covariate, the serum tyrosine level (HR, 1.01; 95% CI, 1.01-1.02) and development of HCC (HR 2.91; 95% CI 1.75-4.81) were independent risk factors for mortality. The serum tyrosine level is an independent risk factor for the development of HCC and mortality in patients with CLD.

Non-small cell lung cancer (NSCLC) remains a major health challenge worldwide, mainly due to the lack of effective early diagnostic biomarkers. Exosome-related genes have recently emerged as potential diagnostic markers due to their roles in tumor progression and immune regulation. This study aimed to identify exosome-related gene signatures as early predictive biomarkers for NSCLC and evaluate their diagnostic and therapeutic significance. We integrated gene expression data from GEO and TCGA databases. Core ExoNSCLC-DEGs were identified using three machine learning methods to construct a NSCLC diagnostic model, and the model was validated using ROC curves, calibration curves, and DCA curves. In addition, immune infiltration analysis, drug enrichment, molecular docking analysis, and regulatory network analysis further explored the potential mechanism of action of ExoNSCLC-DEGs. qRT-PCR experiments verified the reliability of gene expression. We constructed a diagnostic model consisting of six core ExoNSCLC-DEGs (including GPM6A, HYAL1, S100A4, ROBO4, LRRK2, and HBA1). The diagnostic model showed excellent predictive performance in independent cohorts (AUC > 0.98). The calibration curve and DCA curve demonstrated the clinical applicability of the model. Immune infiltration analysis revealed the potential immune effects of some ExoNSCLC-DEGs genes, such as S100A4 and LRRK2, which may play a key role in tumor immune escape. Drug enrichment analysis predicted potential therapeutic compounds, especially sunitinib targeting LRRK2. The regulatory network further identified the key RNA-binding proteins and transcription factors that regulate these biomarkers. qRT-PCR experiments verified the reliability of the expression of ExoNSCLC-DEGs in bioinformatics analysis. The diagnostic model based on the six ExoNSCLC-DEGs has strong diagnostic performance and clinical applicability. In-depth research on ExoNSCLC-DEGs provides new insights into the pathogenesis of NSCLC and provides new directions for subsequent research.

This study proposes a deep learning approach for classifying normal, noninvasive, and invasive urothelial neoplasms via digitized histopathologicalimages. Despite many artificial intelligence (AI) models for cancer diagnosis, few focus on bladder lesions or differentiate between these critical categories. We developed convolutional neural networks (CNNs) and transformer-based models, which were trained on 12,500 whole-slide images (WSIs) from five institutions, with preprocessing steps including stain normalization and patch extraction. Fivefold cross-validation was used for evaluation against expert-annotated labels. Among tested models, EfficientNet-B6 achieved the highest performance, with an accuracy of 0.913 (95% confidence interval (CI), 0.907-0.920), sensitivity of 0.909 (95% CI, 0.904-0.914), specificity of 0.956 (95% CI, 0.953-0.960), F1-score of 0.906 (95% CI, 0.901-0.911), and an area under the receiver operating characteristic curve (AUC) of 0.983 (95% CI, 0.982-0.984). These results demonstrate the effectiveness and generalizability of AI-based bladder cancer classification.

Colorectal cancer (CRC) is a leading causes of cancer-related mortality worldwide. Dysregulated expression of specific genes and non-coding RNAs contributes to CRC progression. This study investigated the expression and clinical relevance of CEACAM6, HOXA-AS3, and miR-29a in CRC, combining experimental data with bioinformatics analysis to assess their diagnostic and prognostic value. Tissue samples from 68 CRC patients (tumor and adjacent normal) were analyzed for CEACAM6, HOXA-AS3, and miR-29a expression by real-time PCR. Bioinformatics validation using TCGA, GEPIA, and ENCORI databases assessed expression, interactions, and assess clinical associations. CEACAM6 and miR-29a were significantly upregulated, while HOXA-AS3 was downregulated in CRC tissues compared to normal counterparts. Notably, miR-29a also showed elevated expression levels in patient serum samples (p < 0.05). Among the examined markers, CEACAM6 expression varied significantly with tumor differentiation status (p < 0.05). Serum levels of IL-6 were significantly increased in CRC patients (p < 0.05). Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy for miR-29a (AUC = 0.918). A significant positive correlation was observed between miR-29a expression in serum and tumor tissue (p = 0.038). Additionally, in silico analysis suggested regulatory interactions between HOXA-AS3 and the mRNAs of CEACAM6 and IL-6. CEACAM6, HOXA-AS3, and miR-29a may serve as promising biomarkers for early detection and prognosis of CRC. Integrating molecular profiling with bioinformatics validation provides a robust approach to uncover clinically relevant targets in CRC. The correlation between serum and tumor tissue miR-29a expression highlights its potential utility in liquid biopsy approaches for CRC.

Colorectal cancer (CRC) screening uptake was low in Singapore. An automated kiosk (KIPFIT) dispensing Faecal Immunochemical Test (FIT) kits was developed to facilitate CRC screening. A prospective observational study leveraged on case-encounter approach to recruit community-dwelling adults aged 50-85 years. They were guided to collect two FIT kits from the kiosk on passing by a local multi-purpose mall. The study aimed to determine their CRC screening uptake by returning minimally one completed kit within two months after its collection. Data on their demographics, awareness, and prior screening history, and kiosk usability (as measured by the System Usability Scale SUS) were analysed using bivariate tests, followed by logistic regression for CRC screening completion and linear regression for SUS scores. Among the 350 participants (mean age 66.1 years; 57.4% female; 91.4% Chinese), 68.9% completed CRC screening, which was associated with Chinese ethnicity (AOR = 3.13, 95%CI = 1.42-6.90) and awareness of screening (AOR = 2.18, 95%CI = 1.10-4.33). Benchmarked at 68, the mean SUS score was 57.7, with lower scores in older and lower-educated participants. Guided use of the KIPFIT kiosk had increased CRC screening uptake. Further research is needed to assess its utility without assistance and its effects on CRC screening in real-world setting.

Frontline high-dose therapy (HDT) is, in 2025, the standard of care for patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT). Prior to high-dose melphalan, induction therapy with quadruplet combinations is also proposed systematically when possible. Lenalidomide maintenance until progression is also recommended per international guidelines. This strategy has been developed over recent decades, based on results of phase 3 trials designed and conducted by different academic groups. With these therapeutic advances, the median overall survival (OS) for patients with MM has increased from 5 years in the 1990s, to over 15 years at present. Here, we present the contribution of the French myeloma cooperative group Intergroupe Francophone du Myélome (IFM) to these advances in the newly diagnosed transplant-eligible (NDTE) setting.

Cutaneous lesions of mastocytosis (CLM) are a hallmark for the diagnosis of mastocytosis. The nomenclature of the term "cutaneous mastocytosis" (CM) is ambiguous as it is used both for classification excluding and as a morphologic description including systemic variants of mastocytosis. Recognition of CLM may be delayed by clinically subtle and very heterogeneous presentations. Distinguishing monomorphic versus polymorphic maculopapular CM may be challenging. Less common presentations require a clearly positive Darier's sign, histopathological confirmation, and/or skin D816V kit mutational analysis. Management of patients with CLM requires multidisciplinary therapy, adequate staging, and follow-up to recognize complications.

To assess the effectiveness of transarterial bland embolization (TAE) compared with transarterial chemoembolization (TACE) therapy in the treatment of patients with intermediate-stage hepatocellular carcinoma (HCC).

A total of 2,031 patients with intermediate-stage HCC were screened, and 1,246 patients who underwent TAE or TACE as the first-choice treatment were retrospectively analyzed and baseline-matched according to the 2 treatment methods. Subgroup analysis was performed among patients according to the Up-to-7 criteria. The primary endpoint was overall survival (OS).

A total of 1,246 patients with HCC who underwent TAE or TACE were included; 720 patients underwent TACE, and 526 underwent TAE. The patients in the TAE group exhibited poorer liver function and a significantly higher rate of hepatitis B infection (P < .001) compared with the TACE group. After propensity score matching, 490 well-matched pairs of patients with intermediate-stage HCC were selected for analysis. Univariate analysis showed that TACE significantly prolonged patient survival compared with TAE (P < .001). The 1-, 2-, and 3-year OS rates were 75.9%, 58.9%, and 44.9% for the TACE group and 59.2%, 34.9%, and 23.8% for the TAE group. Multivariate analysis showed a hazard ratio of 0.556 (95% CI, 0.474-0.653; P < .001) for the TACE approach over the TAE approach for OS. The TACE group had a significantly higher overall response rate than the TAE group (33% vs 26%, P < .001).

TACE resulted in a higher response rate and longer OS compared with TAE as the initial treatment for intermediate-stage HCC.