iSMOD: an integrative browser for image-based single-cell multi-omics data.

Genomic and transcriptomic image data, represented by DNA and RNA fluorescence in situ hybridization (FISH), respectively, together with proteomic data, particularly that related to nuclear proteins, can help elucidate gene regulation in relation to the spatial positions of chromatins, messenger RNAs, and key proteins. However, methods for image-based multi-omics data collection and analysis are lacking. To this end, we aimed to develop the first integrative browser called iSMOD (image-based Single-cell Multi-omics Database) to collect and browse comprehensive FISH and nucleus proteomics data based on the title, abstract, and related experimental figures, which integrates multi-omics studies focusing on the key players in the cell nucleus from 20 000+ (still growing) published papers. We have also provided several exemplar demonstrations to show iSMOD's wide applications-profiling multi-omics research to reveal the molecular target for diseases; exploring the working mechanism behind biological phenomena using multi-omics interactions, and integrating the 3D multi-omics data in a virtual cell nucleus. iSMOD is a cornerstone for delineating a global view of relevant research to enable the integration of scattered data and thus provides new insights regarding the missing components of molecular pathway mechanisms and facilitates improved and efficient scientific research.

Safety and Effectiveness of a Sequential Suture and Plug Vascular Closure Devices Technique for Large-Bore Access Closure after Percutaneous Endovascular Aneurysm Repair.

PURPOSE: To evaluate the safety and effectiveness of sequential sutures and plugged vascular closure devices (VCDs) for large-bore access closure during percutaneous access endovascular aneurysm repair (PEVAR). MATERIALS AND METHODS: Data on 16 patients who underwent PEVAR at the authors' center from January 2022 to May 2022 were retrospectively reviewed. The median age was 72 years (interquartile range [IQR], 59-75 years), with a male-to-female ratio of 3:1. All patients received sequential suture and plug VCDs using dual Exoseal after 1 Proglide for access closure. Success was defined as the ability to achieve complete hemostasis and was confirmed by ultrasonography. The patients were followed up for access-related adverse events at 30 and 90 days after the procedure, and the severity was graded according to the Society of Interventional Radiology (SIR) classification. RESULTS: Overall, 24 access sites were included. The median sheath size was 21 F (IQR, 18-23 F). The median hemostasis time was 11.0 minutes (IQR, 9.3-13.0 minutes), the median procedural time was 133.5 minutes (IQR, 102.5-151.0 minutes), and the median length of stay was 5 days (IQR, 4.0-6.8 days). The success rate was 95.8%, and a pseudoaneurysm (SIR Grade 2) developed in 1 patient, which was treated by a percutaneous injection of thrombin. No other access-related adverse events occurred, and the total adverse event rate was 4.2%. CONCLUSIONS: Placement of sequential suture and plug VCDs using 1 Proglide and dual Exoseal is a safe and effective method and may be an option for access closure during PEVAR.

High-Performance Photochromic Hydrogels for Rewritable Information Record.

Rewritable information record materials usually demand not only reversibly stimuli-responsive ability, but also strong mechanical properties. To achieve one photochromic hydrogel with super-strong mechanical strength, hydrophobic molecule spiropyran (SP) has been introduced into a copolymer based on ion-hybrid crosslink. The hydrogels exhibit both photoinduced reversible color changes and excellent mechanical properties, i.e., the tensile stress of 3.22 MPa, work of tension of 12.8 MJ m-3 , and modulus of elasticity of 8.6 MPa. Moreover, the SP-based Ca2+ crosslinked hydrogels can be enhanced further when exposed to UV-light via ionic interaction coordination between Ca2+ , merocyanine (MC) with polar copolymer chain. In particular, hydrogels have excellent reversible conversion behavior, which can be used to realize repeatable writing of optical information. Thus, the novel design is demonstrated to support future applications in writing repeatable optical information, optical displays, information storage, artificial intelligence systems, and flexible wearable devices.

Insight into the Alkaline Stability of N-Heterocyclic Ammonium Groups for Anion-Exchange Polyelectrolytes.

The alkaline stability of N-heterocyclic ammonium (NHA) groups is a critical topic in anion-exchange membranes (AEMs) and AEM fuel cells (AEMFCs). Here, we report a systematic study on the alkaline stability of 24 representative NHA groups at different hydration numbers (λ) at 80 °C. The results elucidate that γ-substituted NHAs containing electron-donating groups display superior alkaline stability, while electron-withdrawing substituents are detrimental to durable NHAs. Density-functional-theory calculations and experimental results suggest that nucleophilic substitution is the dominant degradation pathway in NHAs, while Hofmann elimination is the primary degradation pathway for NHA-based AEMs. Different degradation pathways determine the alkaline stability of NHAs or NHA-based AEMs. AEMFC durability (from 1 A cm-2 to 3 A cm-2 ) suggests that NHA-based AEMs are mainly subjected to Hofmann elimination under 1 A cm-2 current density for 1000 h, providing insights into the relationship between current density, λ value, and durability of NHA-based AEMs.

Augmentation of miR-202 in varicose veins modulates phenotypic transition of vascular smooth muscle cells by targeting proliferator-activated receptor-γ coactivator-1α.

In varicose veins, vascular smooth muscle cells (VSMCs) often show abnormal proliferative and migratory rates and phenotypic transition. This study aimed to investigate whether microRNA (miR)-202 and its potential target, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were involved in VSMC phenotypic transition. miR-202 expression was analyzed in varicose veins and in VSMCs conditioned with platelet-derived growth factor. The effect of miR-202 on cell proliferation and migration was assessed. Furthermore, contractile marker SM-22α, synthetic markers vimentin and collagen I, and PGC-1α were analyzed by Western blot analysis. The modulation of PGC-1α expression by miR-202 was also evaluated. In varicose veins and proliferative VSMCs, miR-202 expression was upregulated, with decreased SM-22α expression and increased vimentin and collagen I expression. Transfection with a miR-202 mimic induced VSMC proliferation and migration, whereas a miR-202 inhibitor reduced cell proliferation and migration. miR-202 mimic constrained luciferase activity in HEK293 cells that were cotransfected with the PGC-1α 3'-untranslated region (3'-UTR) but not those with mutated 3'-UTR. miR-202 suppressed PGC-1α protein expression, with no influence on its messenger RNA expression. PGC-1α mediated VSMC phenotypic transition and was correlated with reactive oxygen species production. In conclusion, miR-202 affects VSMC phenotypic transition by targeting PGC-1α expression, providing a novel target for varicose vein therapy.

ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression.

Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin-related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE-/- mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE-/- mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression.

Comparison of uncovered stent placement across versus above the main duodenal papilla for malignant biliary obstruction.

PURPOSE: To evaluate the differences in efficiency and complications of metal stent insertion across versus above the main duodenal papilla (MDP) in patients with malignant obstruction of the common bile duct (CBD). MATERIALS AND METHODS: Records of 98 consecutive patients who underwent stent insertion for malignant CBD obstruction between 2004 and 2010 were retrospectively reviewed. Fifty-one patients (group 1) and 47 patients (group 2) were treated with stent insertion across and above the MDP, respectively. Primary stent patency, overall survival, complications, and changes in serum bilirubin level following stent insertion were assessed. RESULTS: Infection appeared in 12 and four patients, respectively, in groups 1 and 2. The respective mean primary stent patency times were 307.8 days ± 20.2 and 490.7 days ± 40.7, and mean survival times were 245.1 days ± 17.4 and 286.3 days ± 20.2. Bilirubin reduction rates were 55.7% ± 16.6 and 61.1% ± 13.7 at 1 week and 84.2% ± 5.7 and 86.2% ± 5.7 at 1 month in groups 1 and 2, respectively. In group 2, the rate of infection was significantly lower (P = .044) and primary stent patency was longer (P = .019). However, there was no significant difference between groups in survival time (P = .074) or bilirubin reduction rate at 1 week (P = .083) or 1 month (P = .082). CONCLUSIONS: Bile stent insertion above the MDP may achieve longer stent patency and a lower infection rate compared with placement across the MDP. For patients with malignant CBD obstruction, biliary stents should be placed above the papilla if papillary lesions are not invaded.

Glycoprotein Ia C807T: Polymorphisms and Their Association with Platelet Function in Patients with the Acute Coronary Syndrome.

OBJECTIVES: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention. MATERIALS AND METHODS: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate. RESULTS: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels. CONCLUSIONS: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment.

Identification of the CD8+ T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data.

The infiltration of CD8+ T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8+ T-cell differential genes were from the TISCH database. We determined 896 CD8+ T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8+ T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8+ T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

Feasibility of a modified hybrid glubran-supported single-proglide technique for access closure during endovascular aneurysm repair.

Objective: This study aimed to evaluate the feasibility of a hybrid Glubran-supported single-Proglide technique for large bore femoral access closure during percutaneous access endovascular aneurysm repair (EVAR). Methods: A retrospective cohort study was performed for all percutaneous EVARs at our center from January 2023 to June 2023. All patients received the hybrid Glubran-supported single-Proglide technique involving a mixture of surgical glue and Lipiodol injection after single suture placement for femoral access closure. Technical success was defined as achieving complete hemostasis without a bailout strategy. Vascular complications and bleeding were defined by Valve Academic Research Consortium-3 (VARC-3) criteria. Vascular access changes and 30-day mortality were recorded. Results: The technique success rate for the entire study population was 100% (55 femoral access in 37 patients; median age: 72; 78% males). The mean sheath size was 20.4 ± 2.3F. The mean manual compression time was 3.5 ± 1.4 min, the mean hemostasis time was 9.0 ± 2.5 min, and the mean procedural time was 103.9 ± 34.7 min. One patient (1.6%) developed an access site infection and recovered conservatively. No VARC-3 vascular complications and access changes were observed. No 30-day mortality happened. Conclusions: The hybrid Glubran-supported single-Proglide technique is feasible for large bore access closure during EVAR and may be a viable alternative; however, larger prospective studies are required to confirm its efficacy.

Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice.

BACKGROUND: Although DNA vaccine holds a great potential for cancer immunotherapy, effective long-lasting antitumoral immunity sufficient to induce durable responses in cancer patients remains to be achieved. Considering the pivotal role of dendritic cells (DC) in the antigen processing and presentation, we prepared DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from NLDC-145 antibody specific for DC-restricted surface molecule DEC-205 (scFvNLDC-145), and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models. RESULTS: In vivo targeting assay demonstrated that scFvNLDC-145 specifically delivered DNA vaccine-encoded antigen to DC. Compared with untargeted HER2/neu DNA vaccines, vaccination with scFvNLDC-145-HER2/neu markedly promoted the HER2/neu-specific cellular and humoral immune responses with long-lasting immune memory, resulting in effective protection against challenge of HER2/neu-positive D2F2/E2 breast tumor while ineffective in parental HER2/neu-negative D2F2 breast tumor. More importantly, in combination with temporary depletion of regulatory T cells (Treg) by low-dose cyclophosphamide, vaccination with scFvNLDC-145-HER2/neu induced the regression of established D2F2/E2 breast tumor and significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice. CONCLUSION: Our findings demonstrate that DC-targeted DNA vaccines for in vivo direct delivery of tumor antigens to DC could induce potent antigen-specific cellular and humoral immune responses and, if additional combination with systemic Treg depletion, was able to elicit an impressively therapeutic antitumoral activity, providing a rationale for further development of this approach for cancer treatment.

Analysis of the association between an insertion/deletion polymorphism within the 3' untranslated region of COL1A2 and chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common cause of leg pain and swelling and is commonly associated with varicose veins. It has significant socioeconomic consequences and is among the most common problems encountered in surgical practice. Although our current understanding of the pathogenesis of CVI is far from clear, there is a growing body of evidence suggesting a genetic contribution to the etiology of CVI. METHODS: By analyzing 254 CVI cases and 508 healthy controls in a Chinese population, we used a candidate gene approach to evaluate the association between a 7-base pair insertion/deletion (indel) polymorphism (rs3917) in the 3' untranslated region (3'UTR) of the alpha-2 type I collagen gene (COL1A2) and CVI susceptibility. Logistic regression was used to analyze the association between rs3917 and CVI risk, adjusted for sex and age. Computational modeling was used to predict potential molecular mechanisms underlying the association. RESULTS: Logistic regression analysis revealed that subjects carrying indel or deletion/deletion genotypes had a significantly increased risk for CVI than individuals carrying insertion/insertion genotypes (adjusted odds ratio, 1.64; 95% confidence interval [CI], 1.10-2.45; P = 0.010). Carrying the 7-base pair deletion allele was associated with a 1.60-fold risk for CVI (95% CI, 1.11-2.31; P = 0.008). Computational modeling suggests that the rs3917 insertion allele lies within a predicted binding site (seed region) for microRNA-382 and that the deletion allele alters the affinity of microRNA-mRNA binding by disrupting the local structure of COL1A2 mRNA, presumably allowing for upregulated COL1A2 expression. CONCLUSIONS: Taken together, our data suggest that common genetic variations in COL1A2 may influence CVI risk, possibly through microRNA-382-mediated regulation. Replication of our studies in other populations will strengthen our understanding of this association.

Downregulation of miR-125a-5p Promotes Endothelial Progenitor Cell Migration and Angiogenesis and Alleviates Deep Vein Thrombosis in Mice Via Upregulation of MCL-1.

Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). MicroRNAs (miRNAs) play regulatory roles in functions of EPCs, which is becoming a promising therapeutic choice for thrombus resolution. The main purpose of this study was to explore the effect of miR-125a-5p on EPC functions in deep vein thrombosis (DVT). EPCs were isolated from the peripheral blood of patients with DVT. In DVT mouse models, DVT was induced by stenosis of the inferior vena cava (IVC). The levels of miR-125a-5p and myeloid cell leukemia sequence 1 (MCL-1) in EPCs and thrombi of DVT mice were detected by RT-qPCR. EPC migration, angiogenesis, and apoptosis were estimated by Transwell assay, tube formation assay, and flow cytometry analysis. Luciferase reporter assay was utilized for detecting the binding of miR-125a-5p and MCL-1. The phosphorylation of PI3K and AKT was estimated by western blot. DVT formation in vivo was observed through hematoxylin-eosin (H&E) staining. The expression of thrombus resolution marker, CD34 molecule (CD34), in the thrombi was measured by immunofluorescence staining. MiR-125a-5p upregulation repressed EPC migration and angiogenesis and facilitated apoptosis. MiR-125a-5p downregulation showed the opposite effect. MCL-1 was targeted and negatively regulated by miR-125a-5p. Additionally, miR-125a-5p inhibited the PI3K/AKT pathway in EPCs. Inhibition of MCL-1 or PI3K/AKT pathway reversed the effect of miR-125a-5p knockdown on EPC functions. The in vivo experiments revealed that miR-125a-5p downregulation repressed thrombus formation and promoted the homing capability of EPCs to the thrombosis site, thereby alleviating DVT mice. Downregulation of miR-125a-5p promotes EPC migration and angiogenesis by upregulating MCL-1, thereby enhancing EPC homing to thrombi and facilitating thrombus resolution.

Micromodification of the Catalyst Layer by CO to Increase Pt Utilization for Proton-Exchange Membrane Fuel Cells.

Improving the utilization of platinum in proton-exchange membrane (PEM) fuel cells is critical to reducing their cost. In the past decade, numerous Pt-based oxygen reduction reaction catalysts with high specific and mass activities have been developed. However, the high activities are mostly achieved in rotating disk electrode (RDE) measurement and have rarely been accomplished at the membrane electrode assembly (MEA) level. The failure of these direct translations from RDE to MEA has been well documented with several key reasons having been previously identified. One of them is the resistance caused by complex mass transport pathways in the MEA. Herein, we improve the proton and oxygen transportations in the MEA by building a thin and uniform distribution of ionomer on the catalyst surface. As a result, a PEM fuel cell design is capable of showing a current density improvement of 38% at the same voltage (0.6 V) under the H2/air operation.

Dual Suture Versus Suture and Plug Closure Devices for Large Bore Access Haemostasis During Percutaneous Access Endovascular Aneurysm Repair.

PURPOSE: This study aimed to compare a dual Proglide strategy versus a combination of one Proglide and dual Exoseal for large-bore access closure during percutaneous access endovascular aneurysm repair (pEVAR). MATERIALS AND METHODS: We retrospectively analyzed 97 patients who underwent pEVAR at our center between January 2021 and February 2023. The patients were divided into two groups: dual Proglide (P + P) and one Proglide with dual Exoseal (P + E). The primary outcome measures were technical success and access-related vascular complications. Technical success was defined as achieving complete hemostasis without a bailout strategy. Postprocedural follow-up for access-related vascular complications was evaluated at 30 and 60 days using computed tomography angiography and ultrasonography. Severity was graded according to the Cardiovascular Interventional Radiological Society of Europe (CIRSE) Classification. RESULTS: Overall, a dual Proglide strategy was used in 46 patients (47.4%) with 65 groins (46.4%), and a combination of one Proglide and dual Exoseal was used in 51 patients (52.6%) with 75 groins (53.6%). The baseline characteristics were similar between the groups. The total technical success rate was 96.4%, and no significant differences were observed (95.4% vs. 97.3%; p = 0.870). Minor bleeding treatable through compression occurred significantly more often in the P group (CIRSE 1, 10.8% vs. 1.3%, p = 0.042). Hemostasis time, procedural time, length of stay in the hospital, closure device failure, and incidence of unplanned intervention did not differ significantly between the groups. CONCLUSIONS: A combined Proglide and Exoseal strategy is safe and effective for large-bore access closure during pEVAR and can be considered an alternative. However, it should be supported by larger prospective studies.

Prognostic signature based on m6A-related lncRNAs to predict overall survival in pancreatic ductal adenocarcinoma.

A growing body of evidence indicates that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play crucial roles in the progression of PDAC and the treatment response of patients with pancreatic ductal adenocarcinoma (PDAC). In this study, we identified m6A-related lncRNAs to reveal their association with PDAC in prognosis and tumor immune environment. A prognostic signature based on 9 m6A-related lncRNAs was established, and the high-risk patients exhibited a significantly worse prognosis than low-risk patients. The predictive capacity was confirmed by receiver operating characteristic (ROC) curve analysis and an independent validation cohort. Correlation analyses revealed that m6A-related lncRNA signature was significantly associated with the number of somatic mutations, immunocyte infiltration, immune function, immune checkpoints, tumor microenvironment (TME) score, and sensitivity to chemotherapeutic drugs. Consequently, we constructed a highly accurate nomogram for improving clinical applicability of signature and exhibited superior predictive accuracy than both the signature and tumor stage. In conclusion, our proposed m6A-related lncRNA signature is a potential indicator predictive of prognosis and immunotherapeutic responses in PDAC patients.

Integrated analysis of senescence-associated genes in pancreatic ductal adenocarcinoma.

Background: Cellular senescence plays a critical role in the occurrence and development, and immune modulation of cancer. This research primarily investigated the role of senescence-associated genes (SAGs) in the survival and tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). Methods: From the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, the gene expression profiles and clinical data of PDAC samples were downloaded. SAGs in the TCGA cohort were used to build a novel prognostic model and validated in the ICGC cohort. The relationship of signature with the immune landscape, tumor mutational burden (TMB), as well as the sensitivity of different therapies, was explored. Moreover, a nomogram was developed to predict the overall survival of PDAC patients. Results: A prognostic signature was constructed on basis of three SAGs, and patients in the low-risk score group had a longer survival time. The accuracy of the signature to distinguish different score groups was confirmed through principal component analysis (PCA) and the Receiver operator curves curve. The mRNA expression of the three signature genes was also verified in normal pancreatic and PDAC cell lines by RT-qPCR. The signature could independently predict the prognosis of PDAC patients and had broad applicability. Meanwhile, the nomogram predicted that 1- and 3-years survival rates were in good agreement with the observed overall survival rates. Low-risk patients had lower tumor mutational burden, and low-TMB patients had a better prognosis. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the low-risk group were more responsive to immunotherapy and a variety of commonly used chemotherapeutic drugs. Conclusion: The prognostic signature can well predict the prognosis and assess the possibility of immunotherapy in personalized PDAC treatment.

Multiomic Analysis of Methylation and Transcriptome Reveals a Novel Signature in Esophageal Cancer.

BACKGROUND: Epigenetic alterations have been shown to lead to human carcinogenesis. The aim of this study was to perform an integrative analysis to develop an epigenetic signature to predict overall survival (OS) of esophageal cancer. METHODS: DNA methylation and messenger RNA expression data of esophageal cancer samples were downloaded from The Cancer Genome Atlas database and were incorporated and analyzed using an R package MethylMix. Functional enrichment analysis of the methylation-related differentially expressed genes (DEGs) was performed. Epigenetic signature and nomogram associated with the OS of esophageal cancer were established by the multivariate Cox model. RESULTS: A total of 71 methylation-related DEGs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these genes were involved in the biological process related to the initiation and progression of esophageal cancer. Two-gene (FAM24B and FAM200A) risk signature for OS was developed by multivariate Cox analysis, of which had high accuracy. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables. Moreover, we developed a novel prognostic nomogram based on risk score and 3 clinicopathological factors. CONCLUSIONS: Our study indicated possible methylation-related DEGs and established an epigenetic signature, which may provide novel insights for understanding the pathogenesis of esophageal cancer.

Is Radical Surgery Alone Enough in T1-3N1a Colon Cancer?

Background: Low lymphatic tumor burden is associated with a better prognosis. However, it is uncertain whether those patients diagnosed as cN0 found to be pN+ could be a favorable subgroup in stage III disease. Radical surgery alone might avoid overtreatment in those patients. Methods: Eligible patients diagnosed with colon cancer without metastasis were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 using SEER*Stat 8.3.5 software (Surveillance Research Program, National Cancer Institute) and divided into two groups: surgery group (n = 3,081) and surgery followed by adjuvant chemotherapy group (n = 4,591). Overall survival (OS) and cause-specific survival (CSS) differences were assessed by Kaplan-Meier analysis, and survival differences were estimated with log-rank tests. Univariate and multivariate Cox proportional hazard regressions were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for colon cancer patients. Results: A total of 7,672 pT1-3N1a colon cancer patients were recruited from 208,751 colon cancer patients. The 5-year CSS rates of patients without and with adjuvant chemotherapy were 80.0 and 90.7%, respectively. The receipt of adjuvant chemotherapy after the radical resection of the primary tumor was independently associated with 57.3% decreased risk of colon cancer-specific mortality compared with surgery alone (HR = 0.427, 95% CI = 0.370-0.492, P < 0.001, using surgery alone as the reference). Conclusions: Adjuvant chemotherapy was significantly associated with improved prognosis and radical surgery alone did not provide enough treatment for colon cancer with very low lymphatic tumor burden.