The identification of heterogeneous reactive oxygen subtypes in esophageal squamous cell carcinoma to aid patient prognosis and immunotherapy.

Introduction: Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients. Methods: A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines. Results: Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines. Conclusion: Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy.

Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma.

BACKGROUND: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. METHODS: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). RESULTS: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell-cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. CONCLUSIONS: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Comprehensive analysis of exosome gene LYPD3 and prognosis/immune cell infiltration in lung cancer.

Background: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. Methods: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. Results: A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. Conclusions: LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

A study on the relationship between recreational physical activity and audiovisual difficulty for older adults.

Audiovisual difficulty are especially common in older adults. Audiovisual difficulty seriously affect the quality of life of older adults in their later years. It is a top priority to find out the related factors, and to intervene and prevent them. The purpose of this study was to explore the relationship between recreational physical activities and audiovisual difficulty in older adults. We hope that older adults can reduce the risk of hearing and visual difficulty through scientific physical activity. A total of 4,886 people were sampled from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. Recreational physical activity was assessed through the Global Physical Activity Questionnaire (GPAQ); Hearing and visual difficulty were assessed using the Disability Questionnaire (DLQ). Chi-square test was used for categorical variables and rank sum test was used for measurement variables. P < 0.05 was considered statistically significant (bilateral test). After univariate analysis, binary Logistic regression analysis was performed with recreational physical activity as the independent variable, statistically significant demographic variable as the covariate, and hearing and visual difficulty as the dependent variable, respectively. (1) After excluding all confounding variables, recreational physical activity was significantly associated with hearing difficulty (P < 0.001), odds ratio (OR) 0.657 (95% CI 0.5899-0.733); (2) Recreational physical activity was significantly associated with visual difficulty (P < 0.001), OR 0.731 (95% CI 0.630-0.849). (1) Recreational physical activity is the protective factor of hearing difficulty in older adults; (2) Recreational physical activity is a protective factor for visual difficulty in older adults.

The association between different types of physical activity and smoking behavior.

BACKGROUND: Smoking is harmful, which has become a major public health burden. Physical activity may be related to smoking. Physical activity is one of the current methods for smoking control and smoking cessation. Different types of physical activity may have different effect on smoking behavior. OBJECTIVE: The purpose of this study was to identify the direction and extent of the impact of different types of physical activity above moderate intensity (including work physical activity, recreational physical activity, commuter physical activity and sedentary behavior) on smoking behavior. MATERIALS AND METHODS: In this study, a total of 2,015 individuals (1,233 males and 782 females, mean age 54.02±17.31 years) was selected from the representative population aged 20 and above in the National Health and Nutrition Survey of the United States from 2017 to 2018. Physical activity was assessed using the Global Physical Activity Questionnaire (GPAQ) ; the tobacco use questionnaire (SMQ) was used to determine whether the sample had smoking behavior at this stage. Binary Logistic regression analysis was performed with various physical activities as independent variables and smoking behavior as dependent variables. All data were analyzed through Statistical Product and Service Solutions (SPSS) 26.0. RESULTS: After adjusted for all confounding variables, physical activity at work was close to significantly associated with smoking behavior (P=0.053), odds ratio (OR) =1.135 (95%Cl: 0.999-1.289). Recreational physical activity was significantly associated with smoking behavior (P < 0.001), OR=0.729 (95%Cl: 0.639-0.832). Commuting physical activity was significantly associated with smoking behavior (P < 0.001), OR=1.214 (95%Cl:1.048-1.405). Sedentary behavior was significantly associated with smoking behavior (P < 0.001), OR=1.363 (95%Cl: 1.154-1.611). CONCLUSIONS: Given that different types of physical activity have different associations with smoking behavior. Therefore, when physical activity is used as a tobacco control measurement, it is necessary to pay attention to the type and environment of physical activity. Recreational physical activities should be appropriately increased, sedentary behavior should be reduced, and smoking prohibit environment should be expanded as far as possible to achieve better clinical intervention effects.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Pyrazine as a More Efficient Luminophore than Benzene for Producing Red-Shifted and Enhanced Photoluminescence.

The development of organic photoluminescent (PL) materials with red-shifted and enhanced emissions is beneficial to promoting their applications. Luminescent materials based on aromatic heterocycles (e.g., pyrazine) usually have red-shifted and enhanced photoluminescence compared with phenyl-based luminescent materials. In this work, the photoluminescence behaviors of pyrazine and its derivatives (o-dichloro-, o-dicyano-, and dichlorodicyano-substituted) are compared with those of benzene and its derivatives. All compounds exhibit fluorescence emissions ranging from blue to yellow, and the fluorescence emissions of pyrazinyl compounds are more red-shifted than those of phenyl compounds. Except for the o-dicyano-substituted compound, pyrazinyl compounds exhibit stronger fluorescence emissions than corresponding phenyl compounds in both pure substances and ethanol solutions. In addition, both 5,6-dichloro-2,3-dicyanopyrazine (P4) and 4,5-dichloro-1,2-dicyanobenzene (B4) exhibit room temperature phosphorescence, and the maximum delayed emission wavelength is red-shifted from 575 nm of B4 to 637 nm of P4. The energy gaps between the highest occupied molecular orbital and the lowest unoccupied molecular orbital of the monomers of pyrazinyl compounds are reduced by 0.07-1.37 eV compared with the monomers of phenyl compounds, which is the fundamental reason for the red-shifted emissions of the pyrazinyl compounds. Moreover, compared to B4, the smaller molecular spacing in the P4 crystal structure facilitates interlayer electron transfer and hence the formation of more extended through-space conjugation, resulting in the red-shifted emission of P4. This work proves that pyrazine is a more efficient luminophore than benzene for constructing PL compounds with longer emission wavelengths and higher quantum yields, which are important in guiding the design and preparation of organic PL materials.

Production of gas-releasing electrolyte-replenishing Ah-scale zinc metal pouch cells with aqueous gel electrolyte.

Aqueous zinc batteries are ideal candidates for grid-scale energy storage because of their safety and low-cost aspects. However, the production of large-format aqueous Zn batteries is hindered by electrolyte consumption, hydrogen gas evolution and accumulation, and Zn dendrites growth. To circumvent these issues, here we propose an "open" pouch cell design for large-format production of aqueous Zn batteries, which can release hydrogen gas and allow the refilling of the electrolyte components consumed during cell cycling. The cell uses a gel electrolyte containing crosslinked kappa (k)-carrageenan and chitosan. It bonds water molecules and hinders their side reaction with Zn, preventing electrolyte leakage and fast evaporation. As a proof-of-concept, we report the assembly and testing of a Zn | |ZnxV2O5·nH2O multi-layer "open" pouch cell using the carrageenan/chitosan gel electrolyte, which delivers an initial discharge capacity of 0.9 Ah and 84% capacity retention after 200 cycles at 200 mA g‒1, 370 kPa and 25 °C.

Machine Learning and Novel Biomarkers Associated with Immune Infiltration for the Diagnosis of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer type, which is related to advanced stage and poor survivals. Therefore, novel diagnostic biomarkers are critically needed. In the current research, we aimed to screen novel diagnostic biomarkers based on machine learning. The expression profiles were obtained from GEO datasets (GSE20347, GSE38129, and GSE75241) and TCGA datasets. Differentially expressed genes (DEGs) were screened between 47 ESCC and 47 nontumor samples. The LASSO regression model and SVM-RFE analysis were carried out for the identification of potential markers. ROC analysis was carried out to assess discriminatory abilities. The expressions and diagnostic values of the candidates in ESCC were demonstrated in the GSE75241 datasets and TCGA datasets. We also explore the correlations between the critical genes and cancer immune infiltrates using CIBERSORT. In this study, we identified 27 DEGs in ESCC: 5 genes were significantly elevated, and 22 genes were significantly decreased. Based on the results of the SVM-RFE and LASSO regression model, we identified five potential diagnostic biomarkers for ESCC, including GPX3, COL11A1, EREG, MMP1, and MMP12. However, the diagnostic values of only GPX3, MMP1, and MMP12 were confirmed in GSE75241 datasets. Moreover, in TCGA datasets, we further confirmed that GPX3 expression was distinctly decreased in ESCC specimens, while the expression of MMP1 and MMP12 was noticeably increased in ESCC specimens. Immune cell infiltration analysis revealed that the expression of GPX3, MMP1, and MMP12 was associated with several immune, such as T cells CD8, macrophages M2, macrophages M0, and dendritic cells activated. Overall, our findings suggested GPX3, MMP1, and MMP12 as novel diagnostic marker and correlated with immune infiltrates in ESCC patients.

The kinetic mechanism of cations induced protein nanotubes self-assembly and their application as delivery system.

The amphiphilic proteins can be used as building blocks (BBs) forming various self-assemblies. Understanding their self-assembly mechanism is important for designing novel nanomaterials. Herein, the BBs dimers were first prepared from carboxyl-abundant enzymolyzed α-lactalbumin (α-lac) at 50 °C. Then the unidentate coordination of Ca2+ between the BBs caused a ß-sheet stacking to further self-assemble into nanotubes (NTs). Compared with the traditional "one-pot" method, a step-wise new method was applied to study hydrolysis, aggregation and self-assembly processes separately. The α-lac was hydrolyzed into 11 kDa amphiphilic peptides independent of temperature while a BBs dimer was formed at 50 °C by hydrophobic interaction. Ca2+ induced a conformational change of BBs and promoted these BBs gradually aggregate into 10 strands of filaments, which twisted into helical ribbons by electrostatic repulsion. Ca2+ further induced the twisted helical ribbons closed into NTs driven by the reduction of line tension energy. Besides, the carboxyl-Ca2+ coordination dominated NTs elongation in the longitudinal direction and filaments aggregation in the lateral direction with the same binding stoichiometry of 1:1 respectively. Finally, NTs successfully encapsulated curcumin and improved the viscosity of liquid food. α-Lac NTs show a high potential as a delivery system for food applications.

Experimental and Numerical Investigation on Oil Displacement Mechanism of Weak Gel in Waterflood Reservoirs.

The production performance of waterflood reservoirs with years of production is severely challenged by high water cuts and extensive water channels. Among IOR/EOR methods, weak gel injection is particularly effective in improving the water displacement efficiency and oil recovery. The visualized microscopic oil displacement experiments were designed to comprehensively investigate the weak gel mechanisms in porous media and the numerical simulations coupling equations characterizing weak gel viscosity induced dynamics were implemented to understand its planar and vertical block and movement behaviors at the field scale. From experiments, the residual oil of initial water flooding mainly exists in the form of cluster, column, dead end, and membranous, and it mainly exists in the form of cluster and dead end in subsequent water flooding stage following weak gel injection. The porous flow mechanism of weak gel includes the preferential plugging of large channels, the integral and staged transport of weak gel, and the residual oil flow along pore walls in weak gel displacement. The profile-control mechanism of weak gel is as follows: weak gel selectively enters the large channels, weak gel blocks large channels and forces subsequent water flow to change direction, weak gel uses viscoelastic bulk motion to form negative pressure oil absorption, and the oil droplets converge to form an oil stream, respectively. The numerical simulation indicates that weak gel can effectively reduce the water-oil mobility ratio, preferentially block the high permeability layer and the large pore channels, divert the subsequent water to flood the low permeability layer, and improve the water injection swept efficiency. It is found numerically that a weak gel system is able to flow forward under high-pressure differences in the subsequent water flooding, which can further improve oil displacement efficiency. Unlike the conventional profile-control methods, weak gels make it possible to displace the bypassed oil in the deep inter-well regions with significant potential to enhance oil recovery.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of MMP12 in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a typical neoplastic disease and a frequent cause of death in China. The prognosis of most ESCC patients is still poor. Previous studies demonstrated that MMP12 is involved in tumor metastasis. However, its clinical significance and association with cancer immunity remained largely unclear. In this study, we first analyzed the expressing pattern of MMPs in ESCC from TCGA datasets and found that several MMPs expression was distinctly increased in ESCC. However, only MMP12 expression was associated with five-year survival of ESCC patients. Then, we focused on MMP12 and found its high expression was positively related to advanced clinical stages of ESCC specimens. KEGG assays revealed MMP12 may influence the activity of several tumor-related pathways, such as the Toll-like receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. Then, we sought to determine whether MMP12 expressions were related to immune cell infiltration in ESCC. We observed that increased MMP12 levels were positively associated with the infiltration levels of mast cells activated and macrophages M0. However, eosinophils, B cells naïve, and mast cells resting exhibited an opposite result. Finally, we showed that knockdown of MMP12 suppressed the proliferation of ESCC cells. Overall, our findings proved that high expression of MMP12 may be a novel and valuable prognostic factor in ESCC.

Bioinformatics Analysis of Prognostic Value of SPC24 in ccRCC and Pan-Cancer.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is one of the most common diseases in the world, with high morbidity and mortality. Recent studies have revealed the important role of SPC24, a subunit of the Ndc80 complex, in the occurrence and development of carcinoma. However, the latent effect of SPC24 in the progress of ccRCC remains to be further explored. The intent of this research is to investigate whether SPC24 can be used as an index to predict the progression of ccRCC and to explore its relationship with the immune microenvironment and pan-cancer. MATERIALS AND METHODS: Based on data from public databases, we determined the expression level and clinical value of SPC24 in ccRCC and human pan-cancer. RT-qPCR analysis was carried out to detect the expression level of SPC24 in the OSRC/786O (human ccRCC cells) cell lines and HK2 (human normal kidney cells) cell line. The signal transduction pathways activated by different levels of SPC24 expression were explored by Gene Set Enrichment Analysis (GSEA), and the CIBERSORT algorithm was applied to analyze the relationship between infiltrating immune cells and SPC24 expression in ccRCC and pan-cancer tissues. RESULTS: SPC24 is overexpressed in ccRCC and several types of tumors, which is associated with poor prognosis. GSEA and CIBERSORT algorithms suggested that the high expression group of SPC24 enriched various pathways including immune-related pathways, and the several infiltrated immunocytes were related to the expression of SPC24. CONCLUSION: Our study revealed that SPC24 is a prognostic factor in ccRCC related to immunomodulation and has generalized value in pan-cancer.

Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer.

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.

Noninvasive Bioluminescence Imaging of Matrix Metalloproteinase-14 Activity in Lung Cancer Using a Membrane-Bound Biosensor.

Matrix metalloproteinase-14 (MMP-14) plays a crucial role in the cancer migration and metastasis by guiding the extracellular matrix remodeling and cell motility. Despite increasing efforts have been taken to develop methodology for measuring MMP-14 expression, there is a lack of tools capable of monitoring the MMP-14 dynamic activity with high temporal and spatial resolution in living cells and animals. Here, we describe the design of Gaussia luciferase (Gluc)-based membrane-bound biosensor for efficient visualization of MMP-14 activity. The epidermal growth factor (EGF) induced significant luciferase changes in the biosensor-transfected lung cancer cells. Deletion of the transmembrane domain in the mutant biosensor or treatment with an MMP-14 inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), relieved the EGF-induced luciferase activation, suggesting that MMP-14 functions at the cell surface to result in luciferase changes. Moreover, utilizing this biosensor, the bioluminescence signals activated by MMP-14 enabled clear visualization of MMP-14-positive lung tumors in animal models. Our results indicated this biosensor is an effective probe for quantitatively monitoring proteolytic activities in live cells and mouse models. These findings offer the general design of biosensors as an adaptable tool for studying various membrane-anchored proteases in biological models.

TEAD4 is an Immune Regulating-Related Prognostic Biomarker for Bladder Cancer and Possesses Generalization Value in Pan-Cancer.

Recent studies have revealed the significant role of TEA domain family member 4 (TEAD4) in the development and progression of cancer. However, the potential role of TEAD4 in the progression of bladder cancer (BC) remains to be explored. The aim of this study was to determine whether TEAD4 could serve as a pan-cancer predictor of the prognosis for BC. Based on data mined from public databases, expression levels and clinical value of TEAD4 were identified in BC and human pan-cancers. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the TEAD4 expression levels in BC cell lines. Gene Set Enrichment Analysis (GSEA) was carried out for functional analysis in BC, and the relationship between infiltrating immune cells and TEAD4 expression was evaluated by the CIBERSORT algorithm in BC and pan-cancer data. TEAD4 was overexpressed and associated with poor prognosis in BC and several types of cancers. GSEA and CIBERSORT algorithm suggested that various pathways including immune-related pathways were enriched in TEAD4 high expression group and several immunocytes infiltrated were correlated with the expression of TEAD4. This study revealed TEAD4 is an immune regulating-related predictor of prognosis for BC and has generalization value in pan-cancer.