ABSTRACT
The specificity and clinical relevance of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa), as well as the effect of androgen deprivation therapy (ADT) on CAFs, remain to be fully elucidated. Using cell lineage diversity and weighted gene co-expression network analysis (WGCNA), we pinpointed a unique CAF signature exclusive to PCa. The specificity of this CAF signature was validated through single-cell RNA sequencing (scRNA-seq), cell line RNA sequencing, and immunohistochemistry. This signature associates CAFs with tumor progression, elevated Gleason scores, and the emergence of castration resistant prostate cancer (CRPC). Using scRNA-seq on collected samples, we demonstrated that the CAF-specific signature is not altered by ADT, maintaining its peak signal output. Identifying a PCa-specific CAF signature and observing signaling changes in CAFs after ADT lay essential groundwork for further PCa studies.
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OBJECTIVE: Infections in patients with kidney stones after extracorporeal shockwave lithotripsy (SWL) is a common clinical issue. However, the associated factors are unclear. Therefore, we aim to develop and validate a predictive model for infections after SWL in patients with kidney stone. METHODS: Between June 2020 and May 2022, consecutive kidney stone patients were enrolled. Of them, 553 patients comprised the development cohort. One hundred sixty-five patients comprised the validation cohort. The data were prospectively collected. The stepwise selection was applied using the likelihood ratio test with Akaike's information criterion as the stopping rule; A predictive model was constructed through multivariate logistic regression. The performance was evaluated regarding discrimination, calibration, and clinical usefulness. RESULTS: Predictors of infections after SWL in treating kidney stones included older age (OR = 1.026, p = 0.041), female (OR = 2.066, p = 0.039), higher BMI (OR = 1.072, p = 0.039), lower stone density (OR = 0.995, p < 0.001), and higher grade of hydronephrosis (OR = 5.148, p < 0.001). For the validation cohort, the model showed good discrimination with an area under the receiver operating characteristic curve of 0.839 (95% CI 0.736, 0.941) and good calibration. Decision curve analysis demonstrated that the model was also clinically useful. CONCLUSION: This study indicated that age, gender, BMI, stone density, and hydronephrosis grade were significant predictors of infections after SWL in treating kidney stones. It provided evidence in optimizing prevention and perioperative treatment strategies to reduce the risk of infection after SWL.
Subject(s)
Hydronephrosis , Kidney Calculi , Lithotripsy , Humans , Female , Prospective Studies , Kidney Calculi/therapy , Lithotripsy/adverse effects , PatientsABSTRACT
Bladder cancer (BC) is a clinical challenge worldwide with late clinical presentation, poor prognosis, and low survival rates. Traditional cystoscopy and tissue biopsy are routine methods for the diagnosis, prognosis, and monitoring of BC. However, due to the heterogeneity and limitations of tumors, such as aggressiveness, high cost, and limited applicability of longitudinal surveillance, the identification of tumor markers has attracted significant attention in BC. Over the past decade, liquid biopsies (e.g., blood) have proven to be highly efficient methods for the discovery of BC biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into the peripheral circulation and allows serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers are being extensively studied and have shown promising results in clinical applications of BC, including early detection, detection of microscopic residual disease, prediction of recurrence, and response to therapy. Therefore, in this review, we aim to provide an update on various novel blood-based liquid biopsy markers and review the advantages and current limitations of liquid biopsy in BC therapy. The role of blood-based circulating tumor cells, circulating tumor DNA, cell-free RNA, exosomes, metabolomics, and proteomics in diagnosis, prognosis, and treatment monitoring, and their applicability to the personalized management of BC, are highlighted.
Subject(s)
Urinary Bladder Neoplasms , Humans , Liquid Biopsy/methods , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/therapy , Biopsy/methods , DNA , Biomarkers, Tumor/geneticsABSTRACT
Agrobacterium tumefaciens is the causal agent of crown gall disease. The bacterium is capable of transferring a segment of single-stranded DNA (ssDNA) into recipient cells during the transformation process, and it has been widely used as a genetic modification tool for plants and nonplant organisms. Transferred DNA (T-DNA) has been proposed to be escorted by two virulence proteins, VirD2 and VirE2, as a nucleoprotein complex (T-complex) that targets the host nucleus. However, it is not clear how such a proposed large DNA-protein complex is delivered through the host nuclear pore in a natural setting. Here, we studied the natural nuclear import of the Agrobacterium-delivered ssDNA-binding protein VirE2 inside plant cells by using a split-GFP approach with a newly constructed T-DNA-free strain. Our results demonstrate that VirE2 is targeted into the host nucleus in a VirD2- and T-DNA-dependent manner. In contrast with VirD2 that binds to plant importin α for nuclear import, VirE2 directly interacts with the host nuclear pore complex component nucleoporin CG1 to facilitate its nuclear uptake and the transformation process. Our data suggest a cooperative nuclear import model in which T-DNA is guided to the host nuclear pore by VirD2 and passes through the pore with the assistance of interactions between VirE2 and host nucleoporin CG1. We hypothesize that this large linear nucleoprotein complex (T-complex) is targeted to the nucleus by a "head" guide from the VirD2-importin interaction and into the nucleus by a lateral assistance from the VirE2-nucleoporin interaction.
Subject(s)
Bacterial Proteins/metabolism , DNA-Binding Proteins/metabolism , Ion Channels/metabolism , Nuclear Pore Complex Proteins/metabolism , Active Transport, Cell Nucleus/physiology , Agrobacterium tumefaciens/genetics , Cell Nucleus/metabolism , DNA, Bacterial/genetics , DNA, Single-Stranded/metabolism , Plant Cells/metabolism , Rhizobium/genetics , Nicotiana/genetics , Transformation, Genetic/genetics , Virulence , Virulence Factors/metabolismABSTRACT
The role of cancer-associated fibroblasts (CAFs) has been thoroughly investigated in tumour microenvironments but not in bladder urothelial carcinoma (BLCA). The cell fraction of CAFs gradually increased with BLCA progression. Weighted gene co-expression network analysis (WGCNA) revealed a specific gene expression module of CAFs that are relevant to cancer progression and survival status. Fifteen key genes of the module were consistent with a fibroblast signature in single-cell RNA sequencing, functionally related to the extracellular matrix, and significant in survival analysis and tumour staging. A comparison of the luminal-infiltrated versus luminal-papillary subtypes and fibroblast versus urothelial carcinoma cell lines and immunohistochemical data analysis demonstrated that the key genes were specifically expressed in CAFs. Moreover, these genes are highly correlated with previously reported CAF markers. In summary, CAFs play a major role in the progression of BLCA, and the 15 key genes act as BLCA-specific CAF markers and can predict CAF changes. WGCNA can, therefore, be used to sort CAF-specific gene set in cancer tissues.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Transitional Cell/genetics , Neoplasm Proteins/genetics , Urinary Bladder Neoplasms/genetics , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Carcinoma, Transitional Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Disease Progression , Female , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Prognosis , RNA-Seq , Single-Cell Analysis , Tumor Microenvironment/genetics , Urinary Bladder Neoplasms/pathology , Urothelium/pathologyABSTRACT
Agrobacterium tumefaciens causes crown gall tumors on various plants by delivering transferred DNA (T-DNA) and virulence proteins into host plant cells. Under laboratory conditions, the bacterium is widely used as a vector to genetically modify a wide range of organisms, including plants, yeasts, fungi, and algae. Various studies suggest that T-DNA is protected inside host cells by VirE2, one of the virulence proteins. However, it is not clear how Agrobacterium-delivered factors are trafficked through the cytoplasm. In this study, we monitored the movement of Agrobacterium-delivered VirE2 inside plant cells by using a split-GFP approach in real time. Agrobacterium-delivered VirE2 trafficked via the endoplasmic reticulum (ER) and F-actin network inside plant cells. During this process, VirE2 was aggregated as filamentous structures and was present on the cytosolic side of the ER. VirE2 movement was powered by myosin XI-K. Thus, exogenously produced and delivered VirE2 protein can use the endogenous host ER/actin network for movement inside host cells. The A. tumefaciens pathogen hijacks the conserved host infrastructure for virulence trafficking. Well-conserved infrastructure may be useful for Agrobacterium to target a wide range of recipient cells and achieve a high efficiency of transformation.
Subject(s)
Actins/metabolism , Bacterial Proteins/metabolism , DNA-Binding Proteins/metabolism , Endoplasmic Reticulum/metabolism , Ion Channels/metabolism , Virulence Factors/metabolism , Agrobacterium tumefaciens/genetics , Agrobacterium tumefaciens/metabolism , Bacterial Proteins/genetics , Brefeldin A/metabolism , Cytochalasin D/metabolism , DNA-Binding Proteins/genetics , Intracellular Space/metabolism , Ion Channels/genetics , Plant Cells/metabolism , Protein Transport , Virulence , Virulence Factors/geneticsABSTRACT
The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3 ). The strategy relies on PMe3 -promoted oxidative addition and transmetalation, and CCl3 CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.
ABSTRACT
A. tumefaciens delivers T-DNA and virulence proteins, including VirE2, into host plant cells, where T-DNA is proposed to be protected by VirE2 molecules as a nucleoprotein complex (T-complex) and trafficked into the nucleus. VirE2 is a protein that can self-aggregate and contains targeting sequences so that it can efficiently move from outside of a cell to the nucleus. We adopted a split-GFP approach and generated a VirE2-GFP fusion which retains the self-aggregating property and the targeting sequences. The fusion protein is fully functional and can move inside cells in real time in a readily detectable format: fluorescent and unique filamentous aggregates. Upon delivery mediated by the bacterial type IV secretion system (T4SS), VirE2-GFP is internalized into the plant cells via clathrin adaptor complex AP2-mediated endocytosis. Subsequently, VirE2-GFP binds to membrane structures such as the endoplasmic reticulum (ER) and is trafficked within the cell. This enables us to observe the highly dynamic activities of the cell. If a compound, a gene, or a condition affects the cell, the cellular dynamics shown by the VirE2-GFP will be affected and thus readily observed by confocal microscopy. This represents an excellent model to study the delivery and trafficking of an exogenously produced and delivered protein inside a cell in a natural setting in real time. The model may be used to explore the theoretical and applied aspects of natural protein delivery and targeting.
Subject(s)
Agrobacterium tumefaciens/metabolism , Agrobacterium tumefaciens/pathogenicity , Bacterial Proteins/metabolism , Host-Pathogen Interactions , Plant Cells/microbiology , Plant Cells/metabolism , Protein Transport , Type IV Secretion Systems , VirulenceABSTRACT
Hoerl & McCormack claim that animals don't represent time. Because this makes a mystery of established findings in comparative psychology, there had better be some important payoff. The main one they mention is that it explains a clash of intuition about the reality of time's passage. But any theory that recognizes the representational requirements of agency can do likewise.
Subject(s)
CognitionABSTRACT
The efficient copper-catalyzed sulfenylation and selenylation of 2,3-allenoic acids with disulfides or diselenides were developed, respectively. These reactions proceeded through tandem radical addition/intramolecular cyclization processes, affording a series of 4-sulfenylated and 4-selenylated butenolides in moderate to excellent yields. Moreover, 4-sulfonylated butenolides could also be obtained by sulfenylation of 2,3-allenoic acids and subsequent oxidation. Further transformation of the sulfur- and selenium-containing butenolides afforded the corresponding furan derivatives in good yields.
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The Type IV Secretion System (T4SS) is the only bacterial secretion system known to translocate both DNA and protein substrates. The VirB/D4 system from Agrobacterium tumefaciens is a typical T4SS. It facilitates the bacteria to translocate the VirD2-T-DNA complex to the host cell cytoplasm. In addition to protein-DNA complexes, the VirB/D4 system is also involved in the translocation of several effector proteins, including VirE2, VirE3 and VirF into the host cell cytoplasm. These effector proteins aid in the proper integration of the translocated DNA into the host genome. The VirD2-binding protein (VBP) is a key cytoplasmic protein that recruits the VirD2-T-DNA complex to the VirD4-coupling protein (VirD4 CP) of the VirB/D4 T4SS apparatus. Here, we report the crystal structure and associated functional studies of the C-terminal domain of VBP. This domain mainly consists of α-helices, and the two monomers of the asymmetric unit form a tight dimer. The structural analysis of this domain confirms the presence of a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) fold. Biophysical studies show that VBP is a dimer in solution and that the HEPN domain is the dimerization domain. Based on structural and mutagenesis analyses, we show that substitution of key residues at the interface disrupts the dimerization of both the HEPN domain and full-length VBP. In addition, pull-down analyses show that only dimeric VBP can interact with VirD2 and VirD4 CP. Finally, we show that only Agrobacterium harboring dimeric full-length VBP can induce tumors in plants. This study sheds light on the structural basis of the substrate recruiting function of VBP in the T4SS pathway of A. tumefaciens and in other pathogenic bacteria employing similar systems.
Subject(s)
Agrobacterium tumefaciens/chemistry , Bacterial Proteins/chemistry , Bacterial Secretion Systems/physiology , Plant Tumors/parasitology , Protein Multimerization , Agrobacterium tumefaciens/metabolism , Amino Acid Sequence , Bacterial Proteins/metabolism , Calorimetry , Circular Dichroism , Crystallography, X-Ray , Host-Parasite Interactions , Kalanchoe/parasitology , Molecular Sequence Data , Protein Multimerization/physiologyABSTRACT
Agrobacterium tumefaciens is a natural genetic engineer widely used to deliver DNA into various recipients, including plant, yeast and fungal cells. The bacterium can transfer single-stranded DNA molecules (T-DNAs) and bacterial virulence proteins, including VirE2. However, neither the DNA nor the protein molecules have ever been directly visualized after the delivery. In this report, we adopted a split-GFP approach: the small GFP fragment (GFP11) was inserted into VirE2 at a permissive site to create the VirE2-GFP11 fusion, which was expressed in A. tumefaciens; and the large fragment (GFP1-10) was expressed in recipient cells. Upon delivery of VirE2-GFP11 into the recipient cells, GFP fluorescence signals were visualized. VirE2-GFP11 was functional like VirE2; the GFP fusion movement could indicate the trafficking of Agrobacterium-delivered VirE2. As the natural host, all plant cells seen under a microscope received the VirE2 protein in a leaf-infiltration assay; most of VirE2 moved at a speed of 1.3-3.1 µm sec⻹ in a nearly linear direction, suggesting an active trafficking process. Inside plant cells, VirE2-GFP formed filamentous structures of different lengths, even in the absence of T-DNA. As a non-natural host recipient, 51% of yeast cells received VirE2, which did not move inside yeast. All plant cells seen under a microscope transiently expressed the Agrobacterium-delivered transgene, but only 0.2% yeast cells expressed the transgene. This indicates that Agrobacterium is a more efficient vector for protein delivery than T-DNA transformation for a non-natural host recipient: VirE2 trafficking is a limiting factor for the genetic transformation of a non-natural host recipient. The split-GFP approach could enable the real-time visualization of VirE2 trafficking inside recipient cells.
Subject(s)
Agrobacterium tumefaciens/genetics , Arabidopsis/cytology , Bacterial Proteins/metabolism , DNA-Binding Proteins/metabolism , Ion Channels/metabolism , Nicotiana/cytology , Saccharomyces cerevisiae/cytology , Arabidopsis/genetics , Arabidopsis/metabolism , Bacterial Proteins/genetics , DNA, Bacterial/genetics , DNA, Single-Stranded/genetics , DNA-Binding Proteins/genetics , Green Fluorescent Proteins , Ion Channels/genetics , Plant Leaves/cytology , Plant Leaves/genetics , Plant Leaves/metabolism , Plants, Genetically Modified , Protein Transport , Recombinant Fusion Proteins , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Nicotiana/genetics , Nicotiana/metabolism , Transgenes , Virulence FactorsABSTRACT
RATIONALE AND OBJECTIVES: This study aims to predict intermediate to high-risk prostate cancer (PCa) prognosis based on 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics. Additionally, subgroup analysis will be performed on the androgen deprivation therapy (ADT) group and the metastatic PCa group. MATERIALS AND METHODS: In the retrospective analysis of 104 intermediate to high-risk PCa patients who underwent 18F-FDG PET/CT prior to treatment. The data set was divided into a training set (n = 72) and a testing set (n = 32). Two different PET/CT models were constructed using multivariate logistic regression with cross-validation: radiomics model A and an alternative ensemble learning-based model B. The superior model was then selected to develop a radiomics nomogram. Separate models were also developed for the ADT and metastatic PCa subgroups. RESULTS: Model A, which integrates eight radiomics features showed excellent performance with an area under curve (AUC) of 0.844 in the training set and 0.804 in the testing set. The radiomics nomogram incorporating the radiomics score (radscore) from model A and the tumor-to-liver ratio (TLR) showed good prognostic accuracy in the testing set with an AUC of 0.827. In the subgroup analyses for endocrine therapy and metastatic cancer, the PET/CT radiomics model showed AUCs of 0.845 and 0.807 respectively, suggesting its potential effectiveness. CONCLUSION: The study establishes the utility of the 18F-FDG PET/CT radiomics nomogram in predicting the prognosis of intermediate to high-risk PCa patients, indicating its potential for clinical application.
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Agrobacterium-mediated transformation is a preferred method for genetic engineering and genome editing of plants due to its numerous advantages, although not all species exhibit transformability. Genetic engineering and plant genome editing methods are technically challenging in recalcitrant crop plants. Factors affecting the poor rate of transformation in such species include host genotype, Agrobacterium genotype, type of explant, physiological condition of the explant, vector, selectable marker, inoculation method, chemical additives, antioxidative compounds, transformation-enhancing compounds, medium formulation, optimization of culture conditions, and pre-treatments. This review provides novel insights into the key factors involved in gene transfer facilitated by Agrobacterium and proposes potential solutions to overcome existing barriers to transformation in recalcitrant species, thereby contributing to improvement programs for these species. This review introduces the key factors that impact the effectiveness of a molecular breeding program using Agrobacterium-mediated transformation, specifically focusing on recalcitrant plant species.
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BACKGROUND: The diagnostic value of combined methylated branched chain amino acid transaminase 1 (BCAT1)/IKAROS family zinc finger 1 (IKZF1) in plasma for colorectal cancer (CRC) has been explored since 2015. Recently, several related studies have published their results and showed its diagnostic efficacy. AIM: To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC. METHODS: The candidate studies were identified by searching the PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases from May 31, 2003 to June 1, 2023. Sensitivity, specificity, and diagnostic accuracy were calculated by merging ratios or means. RESULTS: Twelve eligible studies were included in the analysis, involving 6561 participants. The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60% [95% confidence interval (CI) 53-67] and specificity was 92% (95%CI: 90-94). The positive and negative likelihood ratios were 8.0 (95%CI: 5.8-11.0) and 0.43 (95%CI: 0.36-0.52), respectively. Diagnostic odds ratio was 19 (95%CI: 11-30) and area under the curve was 0.88 (95%CI: 0.85-0.91). The sensitivity and specificity for CRC screening were 64% (95%CI: 59-69) and 92% (95%CI: 91-93), respectively. The sensitivity and specificity for recurrence detection during follow-up were 54% (95%CI: 42-67) and 93% (95%CI: 88-96), respectively. CONCLUSION: The detection of methylated BCAT1/IKZF1 in plasma, as a non-invasive detection method of circulating tumor DNA, has potential CRC diagnosis, but the clinical application prospect needs to be further explored.
Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Humans , Biomarkers, Tumor/genetics , DNA Methylation , Colorectal Neoplasms/pathology , Transaminases , Amino Acids, Branched-Chain/geneticsABSTRACT
Purpose: Acute cholangitis (AC) is a widespread acute inflammatory disease and the main cause of septic shock, which has a high death rate in hospitals. At present, the prediction models for short-term mortality of AC patients are still not ideal. We aimed at developing a new model that could forecast the short-term mortality rate of AC patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). There were a total of 506 cases of AC patients that were included. Patients were given a 7 : 3 split between the training set and the validation set after being randomly assigned to one of the groups. Multivariate logistic regression was used to create an AC patient predictive nomogram for 30-day mortality. The overall efficacy of the model is evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results: Out of 506 patients, 14.0% (71 patients) died. The training cohort had 354 patients, and the validation cohort had 152 patients. GCS, SPO2, albumin, AST/ALT, glucose, potassium, PTT, and peripheral vascular disease were the independent risk factors according to the multivariate analysis results. The newly established nomogram had better prediction performance than other common scoring systems (such as SOFA, OASIS, and SAPS II). For two cohorts, the calibration curve demonstrated coherence between the nomogram and the ideal observation (P > 0.05). The clinical utility of the nomogram in both sets was revealed by decision curve analysis. Conclusion: The novel prognostic model was effective in forecasting the 30-day mortality rate for acute cholangitis patients.
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Global greenhouse gas emissions are increasing when they should be progressively reducing, given worldwide concerted emissions mitigation efforts and protocols. To effectively tackle emissions to foster a sustainable climate, the situation's complexity needs a sector- and region-specific approach, not a one-stop analysis. We must first understand where the emissions originate-which sectors contribute the most to them. This study employs a panel multiregional framework with advanced econometric techniques accounting for cross-sectional dependence and heterogeneous slope coefficients to analyse GHG emissions (CO2 and CH4), sectoral output, economic growth and renewable energy dynamics across African regions from 2010 to 2019. The empirical findings are as follows: First, regional impacts of the economic sectors vary substantially, reflecting technological and socioeconomic differences leading to heterogeneous environmental patterns in the short and long term. Second, the estimated EKC turning points are uniformly lower, indicating slower environmental impact growth with sectoral development in African regions. Third, trade and urbanization are critical drivers of emissions in most regions and economic sectors, with a more pervasive impact on CO2 emissions than CH4 emissions. Finally, sectoral output imposes differential indirect CO2 and CH4 emissions effects via renewable energy, with East African manufacturing exhibiting the most significant emissions-reduction impact. Disaggregated, regional, and sectoral-specific strategies are recommended for designing green development pathways policies.
Subject(s)
Greenhouse Gases , Greenhouse Gases/analysis , Carbon Dioxide/analysis , Economic Development , Cross-Sectional Studies , Renewable EnergyABSTRACT
Background: The RUNX family of transcription factors plays an important regulatory role in tumor development. Although the importance of RUNX in certain cancer types is well known, the pan-cancer landscape remains unclear. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) provides a pan-cancer overview of the RUNX genes. Hence, herein, we performed a pan-cancer analysis of abnormal RUNX expression and deciphered the potential regulatory mechanism. Specifically, we used TCGA multi-omics data combined with multiple online tools to analyze transcripts, genetic alterations, DNA methylation, clinical prognoses, miRNA networks, and potential target genes. Results: RUNX genes are consistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. The total protein expression of RUNX1 in lung adenocarcinoma, kidney renal clear cell carcinoma (KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNA expression results. Moreover, increased phosphorylation on the T14 and T18 residues of RUNX1 may represent potential pathogenic factors. The RUNX genes are significantly associated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma. Meanwhile, various mutations and posttranscriptional changes, including the RUNX1 D96 mutation in invasive breast carcinoma, the co-occurrence of RUNX gene mutations in UCEC, and methylation changes in the RUNX2 promoter in KIRC, may be associated with cancer development. Finally, analysis of epigenetic regulator co-expression, miRNA networks, and target genes revealed the carcinogenicity, abnormal expression, and direct regulation of RUNX genes. Conclusions: We successfully analyzed the pan-cancer abnormal expression and prognostic value of RUNX genes, thereby providing potential biomarkers for various cancers. Further, mutations revealed via genetic alteration analysis may serve as a basis for personalized patient therapies.
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Purpose: The available nomograms used to predict acute pancreatitis (AP) are not comprehensive. We sought to investigate the effect of red blood cell distribution width (RDW)-albumin ratio (RA) on prognosis of patients with AP and develop a new nomogram to identify AP patients at high risk for mortality. Methods: We used data from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). A total of 487 patients with acute pancreatitis were included. Patients enrolled in the study were randomly assigned to the training set and validation set at a 7 : 3 ratio. According to the 30-day mortality rate, the data were divided into a survival group and a death group. Multivariate logistic regression was used to establish a prognostic nomogram for predicting the 30-day mortality in AP patients. The area under the receiver operating characteristic curve (AUC), calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA) are used to verify the overall performance of the model. Results: Among 487 patients, 54 patients died (11.1%). 338 patients were assigned to the training cohort and 149 were assigned to the validation cohort. The multivariate analysis results showed that RA, age, heart rate, temperature, AST/ALT, BUN, hemoglobin, potassium, and bilirubin were independent risk factors. The prediction performance of the newly established nomogram was better than those of other common scoring systems (including SOFA, OASIS, and APSIII). The nomogram suggests that RA (OR = 1.706, 95% CI: 1.367-2.185) is the most significant laboratory test indicator influencing prognosis. Conclusion: The new nomogram incorporating RA performed well in predicting AP short-term mortality. A prospective study with a larger sample is needed to validate our findings.