Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Preparation of High-Purity Docosahexaenoic Acid Ethyl Ester from Algal Oil through Enzymatic Ethanolysis.

Docosahexaenoic acid plays a crucial role in infant brain function, and the market demand of high-purity docosahexaenoic acid is continuously increasing. The availability of docosahexaenoic acid in natural fish oil is limited, prompting the exploration of alternative sources like microalgae. For algal oil, enzymatic ethanolysis is preferred to chemical methods because the former is milder and can avoid docosahexaenoic acid oxidation. However, enzymatic methods have generally low yield due to the poor substrate-specificity of lipase to long-chain polyunsaturated fatty acids, affecting the yield and purity of docosahexaenoic acid. Therefore, we developed an efficient process to produce high-purity docosahexaenoic acid ethyl ester from algal oil, by screening lipases, optimizing enzymatic ethanolysis and applying molecular distillation. Lipase UM1 was the best lipase to produce ethyl ester from algal oil with the highest ethyl ester yield (95.41%). Meanwhile, it was a catalyst for the reaction of long-chain polyunsaturated fatty acids with ethanol. The fatty acid docosahexaenoic acid conversion rates exceeded 90%. After molecular distillation, a final product containing 96.52% ethyl ester was obtained with a docosahexaenoic acid content up to 80.11%. Our findings provide an highly effective enzymatic method for the production of high-purity docosahexaenoic acid ethyl esters, with potential commercial applications.

Enhancement of resistant starch content in ethyl cellulose-based oleogels cakes with the incorporation of glycerol monostearate.

The objective of this work was to completely replace margarine with peanut diacylglycerol oil/ethyl cellulose-glycerol monostearate oleogel (DEC/GMS) oleogel, and evaluate its effect on starch digestibility of cakes. The in vitro digestibility analysis demonstrated that the DEC/GMS-6 cake exhibited a 26.36% increase in slowly digestible starch (SDS) and resistant starch (RS) contents, compared to cakes formulated with margarine. The increased SDS and RS contents might mainly be due to the hydrophobic nature of OSA-wheat flour, which could promote the formation of lipid-amylose complexes with GMS and peanut diacylglycerol oil. XRD pattern suggested that the presence of GMS in DEC-based oleogels facilitated the formation of lipid-amylose complexes. The DSC analysis revealed that the addition of GMS resulted in a significant increase in gelatinization enthalpy, rising from 249.7 to 551.9 J/g, which indicates an improved resistance to gelatinization. The FTIR spectra indicated that the combination of GMS could enhance the hydrogen bonding forces and short-range ordered structure in DEC-based cakes. The rheological analysis revealed that an increase in GMS concentration resulted in enhanced viscoelasticity of DEC-based cake compared to TEC-based cakes. The DEC-based cakes exhibited a more satisfactory texture profile and higher overall acceptability than those of TEC-based cakes. Overall, these findings demonstrated that the utilization of DEC-based oleogel presented a viable alternative to commercial margarine in the development of cakes with reduced starch digestibility.

A novel thermo-responsive phospholipase A1 with high selectivity and efficiency in enzymatic oil degumming.

The limited availability of phospholipase A1 (PLA1) has posed significant challenges in enzymatic degumming. In this study, a novel PLA1 (UM2) was introduced to address this limitation, which had a unique thermo-responsive ability to switch phospholipase and lipase activities in response to temperature variations. Remarkably, UM2 displayed an unprecedented selectivity under optimized conditions, preferentially hydrolyzing phospholipids over triacylglycerols-a specificity superior to that of commercial PLA1. Moreover, UM2 demonstrated high efficiency in hydrolyzing phospholipids with a predilection for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). A practical application of UM2 on crude flaxseed oil led to a dramatic reduction in phosphorus content, plummeting from an initial 384.06 mg/kg to 4.38 mg/kg. Broadening its industrial applicability, UM2 effectively performed enzymatic degumming for other distinct crude vegetable oils with a unique phospholipid composition. Collectively, these results highlighted the promising application of UM2 in the field of oil degumming.

N6-Methyladenosine enhances the translation of ENO1 to promote the progression of bladder cancer by inhibiting PCNA ubiquitination.

The mechanism underlying N6-methyladenosine (m6A) modification in bladder cancer (BC) remains elusive. We identified that the RBM15/METTL3 complex enhances m6A modification and promotes the ENO1 protein translation efficiency through its 359A site by depending on YTHDF1 in BC cells. In the tumor microenvironment, TGF-ß effectively stimulates RBM15/METTL3 expression to improve ENO1 mRNA m6A modification through the Smad2/3 pathway. Reduced ENO1 m6A levels hamper tumor proliferation both in vitro and in vivo. Mechanistically, ENO1 augments PCNA protein stability by reducing its K48-linked ubiquitination and thus prevents protein degradation through the endoplasmic reticulum-associated degradation pathway. According to the subsequent experiments, the ENO1 inhibitor significantly reduced tumor proliferation both in vitro and in vivo. Our study highlights the significance of RBM15/METTL3 complex-mediated ENO1 mRNA m6A modification in ENO1 expression. It also reveals a novel mechanism by which ENO1 promotes BC progression, thereby suggesting that ENO1 can be a therapeutic target for BC.

Tumor-associated macrophage enhances PD-L1-mediated immune escape of bladder cancer through PKM2 dimer-STAT3 complex nuclear translocation.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME) and strongly associated with poor prognosis and drug resistance, including checkpoint blockade immunotherapy in solid tumor patients. However, the mechanism by which TAM affects immune metabolism reprogramming and immune checkpoint signalling pathway in the TME remains elusive. In this study we found that transforming growth factor-beta (TGF-ß) secreted by M2-TAMs increased the level of glycolysis in bladder cancer (BLCA) and played important role in PD-L1-mediated immune evasion through pyruvate kinase isoenzymes M2 (PKM2). Mechanistically, TGF-ß promoted high expression of PKM2 by promoting the nuclear translocation of PKM2 dimer in conjunction with phosphorylated signal transducer and activator of transcription (p-STAT3), which then exerted its kinase activity to promote PD-L1 expression in BLCA. Moreover, SB-431542 (TGF-ß blocker) and shikonin (PKM2 inhibitor) significantly reduced PD-L1 expression and inhibited BLCA growth and organoids by enhancing anti-tumor immune responses. In conclusion, M2-TAM-derived TGF-ß promotes PD-L1-mediated immune evasion in BLCA by increasing the PKM2 dimer-STAT3 complex nuclear translocation. Combined blockade of the TGF-ß receptor and inhibition of PKM2 effectively prevent BLCA progression and immunosuppression, providing a potential targeted therapeutic strategy for BLCA.

Identification and validation of a signature based on myofibroblastic cancer-associated fibroblast marker genes for predicting prognosis, immune infiltration, and therapeutic response in bladder cancer.

PURPOSE: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). MATERIALS AND METHODS: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. RESULTS: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. CONCLUSIONS: Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Testicular metastasis from urothelial carcinoma: case report and literature review.

Urothelial carcinoma (UC) with testicular metastasis is extremely rare, and its modes of metastasis, prognosis, and treatment are unclear. In this report, we present an extraordinarily rare case of testicular metastasis arising from UC 8 years after surgery. The patient underwent left orchiepididymectomy and received immunotherapy postoperatively. After a 6-month follow-up, there were no signs of recurrence. Moreover, the clinical characteristics, metastasis pattern, and treatment plan were also summarized based on 14 earlier reported cases of UC with testicular metastasis.

Microtubule interacting and trafficking domain containing 1 deficiency leads to poor survival via tissue factor-mediated coagulation in bladder cancer.

BACKGROUND: Patients with cancer are at an increased risk of developing a hypercoagulative phenotype and venous thromboembolism. However, no clinical trial has yet confirmed that anticoagulant therapy improves cancer prognosis, and the mechanism underlying hypercoagulation in patients with bladder cancer is not well understood. OBJECTIVES: We hypothesized that the prognostic genes affect tumor progression via tumor-mediated coagulation. METHODS: We detected the most significant prognostic genes of bladder cancer with The Cancer Genome Atlas dataset and validated them in 2 Gene Expression Omnibus datasets and 1 ArrayExpress dataset. Immunohistochemical tests were performed on a cohort of 80 individuals to further examine the prognostic genes. For the most reliable prognostic gene, its influence on coagulation was evaluated with gene knockdown followed by next-generation sequencing and cellular and animal experiments. RESULTS: Depletion of microtubule interacting and trafficking domain containing 1 (MITD1), a major prognostic gene of bladder cancer, significantly increased the tissue factor (TF) expression. MITD1 deficiency led to cytokinesis arrest, which, in turn, promoted the TF expression via unfolded protein response and c-Jun. The knockdown of IRE1, an essential kinase of unfolded protein response or the inactivation of c-Jun using c-Jun N-terminal kinase inhibitors weakened MITD1 deficiency- or dithiothreitol-induced TF upregulation. Cells lacking MITD1 promoted coagulation and metastasis in the experimental metastasis assay. CONCLUSION: Our findings suggest the novel role of tumor prognostic genes upon the development of hypercoagulative phenotype and venous thromboembolism, thereby underlining the importance of anticoagulant therapy and shedding light on the therapeutic value of targeting MITD1 in bladder cancer.

Molecular mechanism of NAD+ and NMN binding to the Nudix homology domains of DBC1.

Deleted in breast cancer 1 (DBC1) is a human nuclear protein that modulates the activities of various proteins involved in cell survival and cancer progression. Oxidized form of nicotinamide adenine dinucleotide (NAD+) is suggested to bind to the Nudix homology domains (NHDs) of DBC1, thereby regulating DBC1-Poly (ADP-ribose) polymerase 1 (PARP1) interactions, resulting in the restoration of DNA repair. Using Nuclear Magnetic Resonance (NMR) and Isothermal Titration Calorimetry (ITC), we confirmed NAD+ and its precursor nicotinamide mononucleotide (NMN) both bind the NHD domain of DBC1 (DBC1354-396). NAD+ likely interacts with DBC1354-396 through hydrogen bonding, with a binding affinity (8.99 µM) nearly twice that of NMN (17.0 µM), and the key binding sites are primarily residues E363 and D372, in the agreement with Molecular Docking experiments. Molecular Dynamics (MD) simulation further demonstrated E363 and D372's anchoring role in the binding process. Additional mutagenesis experiments of E363 and D372 confirmed their critical involvement of ligand-protein interactions. These findings lead to a better understanding of how NAD+ and NMN regulate DBC1, thereby offering insights for the development of targeted therapies and drug research focused on DBC1-associated tumors.

Exploring Diacylglycerol Oil-Based Oleogels as Effective Stabilizers in Peanut Butter: Performance, Structural Insights, and Sensory Evaluation.

In the pursuit of reducing oil separation in peanut butter, oleogels synthesized from diacylglycerol (DAG)-rich peanut oils, using glycerol monostearate (GMS) as the gelator, were examined as alternative stabilizers. In comparison to triacylglycerol (TAG)-rich peanut oils, the DAG oil-based oleogels exhibited better oil-binding capacities across increasing GMS concentrations. Intriguingly, thermal and rheological assessments pointed to a weaker network structure in DAG oil oleogels, as evidenced by their lower crystallization temperatures and reduced viscoelastic parameters (G' and G''). Insight from infrared spectroscopy revealed that this could stem from heightened intermolecular hydrogen bonding between the DAG oil and the gelator. When applied to peanut butter, DAG oil oleogels demonstrated efficacy in minimizing oil separation. Extended storage trials affirmed the long-term stability of peanut butter formulations incorporating these oleogels. Furthermore, sensory evaluations by panelists underscored favorable impressions, suggesting potential consumer acceptance. Overall, this study illuminates the promising role of DAG oleogels as effective, alternative stabilizers in peanut butter formulations.

Efficient Enzymatic Enrichment of High-purity Nervonic Acid from Malania oleifera Seed Oil.

Nervonic acid (NA) is a monounsaturated fatty acid vital for brain health and is of emerging importance in various industrial applications, including therapeutics, food, and cosmetics. Given the growing demands of the food and pharmaceutical industries, there's a pressing need for high-purity NA. Previously, NA constituents in plant seed oils were chemically transformed into nervonic acid ethyl ester (NAEE) to facilitate extraction from seed oils. In this study, we present an enzymatic approach to convert NA constituents in Malania oleifera seed oil to NAEE. Combined with the utilization of the semi-preparative chromatography, we achieved a remarkable purity of 97.52% NAEE. Compared to conventional chemical preparations characterized by multiple steps, prolonged processing times, and low yields and purities, our enzymatic method stands out as a more efficient and advantageous alternative. On top of that, this innovative approach is environmentally friendly and circumvents health and safety issues associated with chemical processes.

Modification of lysine-260 2-hydroxyisobutyrylation destabilizes ALDH1A1 expression to regulate bladder cancer progression.

ALDH1A1 is one of the classical stem cell markers for bladder cancer. Lysine 2-hydroxyisobutyrylation (Khib) is a newfound modification to modulate the protein expression, and the underlying mechanisms of how ALDH1A1 was regulated by Khib modification in bladder cancer remains unknown. Here, ALDH1A1 showed a decreased K260hib modification, as identified by protein modification omics in bladder cancer. Decreasing ALDH1A1 expression significantly suppressed the proliferation, migration and invasion of bladder cancer cells. Moreover, K260hib modification is responsible for the activity of ALDH1A1 in bladder cancer, which is regulated by HDAC2/3. Higher K260hib modification on ALDH1A1 promotes protein degradation through chaperone-mediated autophagy (CMA), and ALDH1A1 K260hib could sensitize bladder cancer cells to chemotherapeutic drugs. Higher ALDH1A1 expression with a lower K260hib modification indicates a poor prognosis in patients with bladder cancer. Overall, we demonstrated that K260hib of ALDH1A1 can be used as a potential therapeutic target for bladder cancer treatment.

Physicochemical properties and feasibility of coconut oil-based diacylglycerol as an alternative fat for healthy non-dairy creamer.

Non-dairy creamers have been widely used for coffee whitening and texture improvement. To avoid the intake of trans fatty acids from partially hydrogenated oil, coconut oil-based diacylglycerol (CO-DAG) was applied in non-dairy creamer as core material. In this study, effects of DAG content (30, 50, 70, 90%) on the characteristics of CO-DAG were evaluated, including rheological and thermodynamic properties. The CO-DAG with a content of 50% exhibited a wide plastic range and contained mixture of ß and ß' polymorphic forms. Using CO-DAG (50%) as core material, the physicochemical properties of non-dairy creamer were characterized and compared with commercial products. The results indicated that CO-DAG-based non-dairy creamers showed similar encapsulation efficiency (92.74%) and thermal stability to commercial products. Furthermore, CO-DAG-based non-dairy creamer showed higher whiteness index (54.20) than commercial non-dairy creamers (50.22) when applied to black coffee. Overall, it is anticipated that CO-DAG-based non-dairy creamers have great potentials in coffee whitening.

Enhanced wide-range gas pressure sensing with an all-solid open Fabry-Pérot interferometer.

The sensors with a wide gas pressure detection range are urgently demanded in many industrial applications. Here, we propose a gas pressure sensor based on an all-solid open Fabry-Pérot interferometer, which is prepared by using optical contact bonding to ensure high structural strength and high-quality factor of 8.8 × 105. The applied pressure induces a change in the refractive index of the air, leading to the shift of the resonant spectrum. The pressure is detected by calibrating this shift. The sensor exhibits a pressure sensitivity of 4.20 ± 0.01 nm/MPa in a pressure range of 0 to 10 MPa and has a minimum pressure resolution of 0.005 MPa. Additionally, it shows a lower temperature cross-sensitivity of -0.25 kPa/°C. These findings affirm that the sensor achieves high-sensitivity pressure sensing across a wide detection range. Moreover, owing to its exceptional mechanical strength, it holds great promise for applications in harsh environments, such as high temperature and high pressure.

Quality characteristics of peanut protein-based patties produced with pre-emulsified olive oil as a fat replacer: Influence of acylglycerol type.

The emulsion (O/W) may be used as a fat replacer to develop healthier meat analogs. The purpose of this work was to evaluate the effects of oil incorporation methods (direct oil addition and emulsion addition) and oil types [triacylglycerol (TAG) and diacylglycerol (DAG)] on the quality characteristics of peanut protein-based patties crosslinked by transglutaminase (TGase). The patties formulated with emulsions showed larger texture parameters (springiness, cohesiveness and gumminess), lower cooking loss and higher acceptability compared with directly adding oil. The rheological results confirmed that the presence of emulsions strengthened the gel structure in patties, which allowed the patties containing emulsions to stabilize free water. Whereas, TAG-based emulsion was more effective than DAG-based emulsion in improving quality of products, possibly because the competitive adsorption at oil-water interface of DAG reduced the crosslinking between the interfacial protein and adjacent protein molecules. This study revealed the relationship between the acylglycerol type in emulsion and the patty quality, providing a reference for the development of plant-based patties.

A feed-forward loop based on aerobic glycolysis and TGF-ß between tumor-associated macrophages and bladder cancer cells promoted malignant progression and immune escape.

PURPOSE: Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has revolutionized the systemic treatment of solid tumors, including bladder cancer. Previous studies have shown that enhanced glycolysis, tumor-associated macrophage (TAM) infiltration, and TGF-ß secretion in the tumor microenvironment (TME) are closely related to PD-1/PD-L1 inhibitor immunotherapy resistance. However, the potential mechanism of their interaction in bladder cancer has not been fully uncovered. METHODS: By coculturing bladder cancer cells and TAMs, we studied the relationship and interaction mechanism between tumor cell glycolysis, TAM functional remodeling, TGF-ß positive feedback secretion, and PD-L1 mRNA m6A methylation in the bladder cancer microenvironment. RESULTS: Bioinformatics analysis and IHC staining found a close correlation between tumor glycolysis, M2 TAM infiltration, and the prognosis of bladder cancer patients. In Vitro experiments demonstrated that bladder cancer cells could re-educate M2 TAMs through lactate and promote TGF-ß secretion via the HIF-1α signaling pathway. Reciprocally, in vitro, and in vivo experiments validated that M2 TAMs could promote glycolysis in bladder cancer cells by TGF-ß via the Smad2/3 signaling pathways. Furthermore, M2 TAMs could also promote CSCs and EMT of bladder cancer cells. More importantly, we found M2 TAMs enhance PD-L1 mRNA m6A methylation by promoting METLL3 expression in bladder cancer via the TGF-ß/Smad2/3 pathway in the TME. CONCLUSIONS: Our study highlights a feed-forward loop based on aerobic glycolysis and TGF-ß between M2 TAMs and bladder cancer cells, which may be a potential mechanism of malignant progression and immunotherapy resistance in bladder cancer.

Enzymatic Interesterification of Palm Stearin, Flaxseed Oil and Cottonseed Stearin to Produce Stable Plastic Fat with Balanced Omega-6 and Omega-3 Fatty Acids.

This study aimed to produce stable plastic fat with desired physicochemical characteristics and ω-6/ω-3 fatty acid ratio (1:1-4:1) from palm stearin (PS), flaxseed oil (FSO) and cottonseed stearin (CS) via enzymatic interesterification (EIE). For the first time, the EIE variables of the blends containing PS, FSO and CS were investigated and optimized through single-factor experiments and response surface design to achieve a high interesterification degree. The optimized enzymatic interesterification conditions were: 60°C, 6 wt% Lipase UM1, and 6 h. Lipase UM1 had a similar effect on ID values with commercial lipases. The EIE improved the compatibility of the lipid blends, with the interesterified product EIE-721 (7:2:1, PS: FSO:CS) being the best candidate base stock for shortening considering its solid fat content, desired ω-6/ω-3 fatty acid ratio, wide melting range, abundant ß' form crystal, and compact microstructure. This study provides a strategy to produce balanced ω-6/ω-3 fatty acid plastic fat through enzymatic interesterification and validates the application of Lipase UM1 in the preparation of plastic fat.

Comparison of outcomes between tubular microdiscectomy and conventional microdiscectomy for lumbar disc herniation: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The clinical outcomes of using a tubular microdiscectomy for lumbar disc herniation were evaluated by comparison with conventional microdiscectomy. METHODS: All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 May 2023 were included. All outcomes were analysed using Review Manager 5.4. RESULTS: This meta-analysis included four randomized controlled studies with a total of 523 patients. The results showed that using tubular microdiscectomy for lumbar disc herniation was more effective than conventional microdiscectomy in improving the Oswestry Disability Index (P < 0.05). However, there were no significant differences in operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate (all P > 0.05) between the tubular microdiscectomy and conventional microdiscectomy groups. CONCLUSIONS: Based on our meta-analysis, it was found that the tubular microdiscectomy group had better outcomes than the conventional microdiscectomy group in terms of Oswestry Disability Index. However, there were no significant differences between the two groups in terms of operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate. Current research suggests that tubular microdiscectomy can achieve clinical results similar to those of conventional microdiscectomy. PROSPERO registration number is: CRD42023407995.

Integrated multiomics analysis and machine learning refine molecular subtypes and prognosis for muscle-invasive urothelial cancer.

Muscle-invasive urothelial cancer (MUC), characterized by high aggressiveness and significant heterogeneity, is currently lacking highly precise individualized treatment options. We used a computational pipeline to synthesize multiomics data from MUC patients using 10 clustering algorithms, which were then combined with 10 machine learning algorithms to identify molecular subgroups of high resolution and develop a robust consensus machine learning-driven signature (CMLS). Through multiomics clustering, we identified three cancer subtypes (CSs) that are related to prognosis, with CS2 exhibiting the most favorable prognostic outcome. Subsequent screening enabled identification of 12 hub genes that constitute a CMLS with robust predictive power for prognosis. The low-CMLS group exhibited a more favorable prognosis and greater responsiveness to immunotherapy and was more likely to exhibit the "hot tumor" phenotype. The high-CMLS group had a poor prognosis and lower likelihood of benefitting from immunotherapy, but dasatinib and romidepsin may serve as promising treatments for them. Comprehensive analysis of multiomics data can offer important insights and further refine the molecular classification of MUC. Identification of CMLS represents a valuable tool for early prediction of patient prognosis and for screening potential candidates likely to benefit from immunotherapy, with broad implications for clinical practice.