ANALYSIS ON INFILTRATIVE CHARACTERISTICS OF DEFORMABLE POROUS MATAL RUBBER MATERIAL AND PARAMATERS IDENTIFICATION

The effect of deformation of porous material on infiltrative performance is investigated. Based on Darcy theory and Boit principle, the Reynolds equation and mathematical expression of deformable metal rubber （MR） material under laminar flow are obtained according to the change of porosity of metal rubber. It is shown that the throttle of MR material is dependent on its porosity and diameter of metal wires. It will be of great value for the application of MR in throttle field.

Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis

BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer(IGC)remain unknown.AIM To elucidate the molecular characteristics of IGC at the proteomics level.METHODS Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry.The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software.The differentially expressed proteins(DEPs)were screened using|log2(Fold change)|>1 and P-adj<0.01 as the thresholds.The expression levels of selected proteins were verified by Western blotting.The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software.The DEPs were functionally annotated using clusterProfiler,STRING and DAVID for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways.P<0.05 was considered statistically significant.RESULTS A total of 7361 DEPs were identified,of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues.The top 10 up-regulated proteins were MRTO4,BOP1,PES1,WDR12,BRIX1,NOP2,POLR1C,NOC2L,MYBBP1A and TSR1,and the top 10 down-regulated proteins were NDUFS8,NDUFS6,NDUFA8,NDUFA5,NDUFC2,NDUFB8,NDUFB5,NDUFB9,UQCRC2 and UQCRC1.The up-regulated proteins were enriched for 9 biological processes including DNA replication,ribosome biogenesis and initiation of DNA replication,and the cellular component MCM complex.Among the down-regulated proteins,17 biological processes were enriched,including glucose metabolism,pyruvic acid metabolism and fatty acidβ-oxidation.In addition,the mitochondrial inner membrane,mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components,and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity,acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched.The significant KEGG pathways for the up-regulated proteins were DNA replication,cell cycle and mismatch repair,whereas 18 pathways including oxidative phosphorylation,fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins.CONCLUSION The proteins involved in cell cycle regulation,DNA replication and mismatch repair,and metabolism were significantly altered in IGC,and the proteomic profile may enable the discovery of novel biomarkers.

Repeated operations for infiltrative low - grade gliomas without intervening therapy.

OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.

ERBB1 Is Amplified and Overexpressed in High-grade Diffusely Infiltrative Pediatric Brain Stem Glioma

PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,

Prognostic significance of serum inflammation indices for different tumor infiltrative pattern types of gastric cancer

BACKGROUND Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer(GC).However,there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern(INF)types.AIM To evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC.METHODS A total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study.Patients were categorized into the expansive growth type(INFa),the intermediate type(INFb),and the infiltrative growth type(INFc)groups.The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves.The Kaplan–Meier method and log-rank test were used to analyze overall survival(OS).The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics.The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression.Nomogram models were constructed by R studio.RESULTS The INFc group had the worst OS(P<0.001).The systemic immune-inflammation index(P=0.039)and metastatic lymph node ratio(mLNR)(P=0.003)were independent risk factors for prognosis in the INFa group.The platelet-lymphocyte ratio(PLR)(P=0.018),age(P=0.026),body mass index(P=0.003),and postsurgical tumor node metastasis(pTNM)stage(P<0.001)were independent risk factors for prognosis in the INFb group.The PLR(P=0.021),pTNM stage(P=0.028),age(P=0.021),and mLNR(P=0.002)were independent risk factors for prognosis in the INFc group.The area under the curve of the nomogram model for predicting 5-year survival in the INFa group,INFb group,and INFc group was 0.787,0.823,and 0.781,respectively.CONCLUSION The outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.

Effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer

Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer who accepted bladder infusion chemotherapy in Wuhan Red Cross Hospital between March 2015 and August 2016 were selected and randomly divided into the IFN-α+GEM group and the GEM group who acceptedα-interferon + gemcitabine combined with infusion chemotherapy and single gemcitabine infusion chemotherapy respectively. The contents of bladder cancer markers, cancer cell apoptosis molecules and angiogenesis molecules in urine were detected before treatment and 3 months after treatment. Results: 3 months after treatment, NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of both groups of patients were significantly lower than those before treatment while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those before treatment, and NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of IFN-α+GEM group were significantly lower than those of GEM group while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those of GEM group. Conclusion: α-interferon + gemcitabine combined with infusion chemotherapy can be more effective than single gemcitabine infusion chemotherapy in killing cancer cells and inhibiting the proliferation and infiltrative growth of the cancer cells.

Surrogate modeling for unsaturated infiltration via the physics and equality-constrained artificial neural networks

Machine learning(ML)provides a new surrogate method for investigating groundwater flow dynamics in unsaturated soils.Traditional pure data-driven methods(e.g.deep neural network,DNN)can provide rapid predictions,but they do require sufficient on-site data for accurate training,and lack interpretability to the physical processes within the data.In this paper,we provide a physics and equalityconstrained artificial neural network(PECANN),to derive unsaturated infiltration solutions with a small amount of initial and boundary data.PECANN takes the physics-informed neural network(PINN)as a foundation,encodes the unsaturated infiltration physical laws(i.e.Richards equation,RE)into the loss function,and uses the augmented Lagrangian method to constrain the learning process of the solutions of RE by adding stronger penalty for the initial and boundary conditions.Four unsaturated infiltration cases are designed to test the training performance of PECANN,i.e.one-dimensional(1D)steady-state unsaturated infiltration,1D transient-state infiltration,two-dimensional(2D)transient-state infiltration,and 1D coupled unsaturated infiltration and deformation.The predicted results of PECANN are compared with the finite difference solutions or analytical solutions.The results indicate that PECANN can accurately capture the variations of pressure head during the unsaturated infiltration,and present higher precision and robustness than DNN and PINN.It is also revealed that PECANN can achieve the same accuracy as the finite difference method with fewer initial and boundary training data.Additionally,we investigate the effect of the hyperparameters of PECANN on solving RE problem.PECANN provides an effective tool for simulating unsaturated infiltration.

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.

Predicting Infiltrative Hepatocellular Carcinoma Patient Outcome Post-TACE:MR Bias Field Correction Effect on 3D-quantitative Image Analysis

Background and Aims:To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carcinoma,after transcatheter arterial chemoembolization(TACE).Methods:This study included 101 patients treated with conventional or drug-eluting beads TACE between the years of 2001 and 2013.Semi-automated 3D quantification software was used to segment and calculate the enhancing tumor volume(ETV)of the liver with and without bias-field correction on multi-phasic contrast-enhanced MRI before and 1-month after initial TACE.ETV(expressed as cm3)at baseline imaging and the relative change in ETV(as%change,ETV%)before and after TACE were used to predict response and survival,respectively.Statistical survival analyses included Kaplan-Meier curve generation and Cox proportional hazards modeling.Q statistics were calculated and used to identify the best cut-off value for ETV to separate responders and non-responders(ETV cm3).The difference in survival was evaluated between responders and non-responders using Kaplan-Meier and Cox models.Results:MR bias field correction correlated with improved response calculation from baseline MR as well as survival after TACE;using a 415 cm3 cut-off for ETV at baseline(hazard ratio:2.00,95%confidence interval:1.23-3.26,p=0.01)resulted in significantly improved response prediction(median survival in patients with baseline ETV<415 cm3:19.66 months vs.≥415 cm3:9.21 months,p<0.001,log-rank test).A≥41%relative decrease in ETV(hazard ratio:0.58,95%confidence interval:0.37-0.93,p=0.02)was significant in predicting survival(ETV≥41%:19.20 months vs.ETV<41%:8.71 months,p=0.008,log-rank test).Without MR bias field correction,response from baseline ETV could be predicted but survival after TACE could not.Conclusions:MR bias field correction improves both response assessment and accuracy of survival prediction using whole liver tumor enhancement analysis from baseline MR after initial TACE in patients with infiltrative hepatocellular carcinoma.

GIS-based prediction method of shallow landslides induced by heavy rainfall in large mountainous areas

Rainwater runoff that does not infiltrate the soil during heavy rainfall may increase slope instability. The effect of runoff is usually neglected in conventional rainfall-induced slope failure analysis to simplify the model. To analyze the effect of runoff on slope stability, this study simultaneously simulated the effects of surface runoff and rainfall infiltration on bank slopes in the Three Gorges Reservoir Area. A shallow slope failure method that can be used to analyze runoff was proposed based on the modified Green-Ampt model, the simplified Saint-Venant model, and the infinite slope model. In this model, the modified Green–Ampt model was used to estimate the rainfall infiltration capacity and the wetting front depth. The eight-flow(D8) method and the simplified Saint-Venant model were selected to estimate the distribution of runoff. By considering the wetting front depth as the slip surface depth, the factor of safety of the slope could be determined using the infinite slope stability model. A comparison of the different models reveals that runoff can escalate the instability of certain slopes, causing stable slopes to become unstable. Comparison of the unstable areas obtained from the simulation with the actual landslide sites shows that the model proposed in this study can successfully predict landslides at these sites. The slope instability assessment model proposed in this study offers an alternative approach for estimating high-risk areas in large mountainous regions.

NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

Effect of microalloying on wettability and interface characteristics of Zr-based bulk metallic glasses with W substrate

The infiltration casting method is widely employed for the preparation of ex-situ composite materials.However,the production of composite materials using this method must necessitates a comprehensive understanding of the wettability and interface characteristics between the reinforcing phase and the bulk metallic glasses(BMGs).This work optimized the composition of Zr-based BMGs through microalloying methods,resulting in a new set of Zr-based BMGs with excellent glass-forming ability.Wetting experiments between the Zr-based BMGs melts and W substrates were conducted using the traditional sessile drop method,and the interfaces were characterized utilizing a scanning electron microscope(SEM)equipped with energy dispersive X-ray spectroscopy(EDS).The work demonstrates that the microalloying method substantially enhances the wettability of the Zr-based BMGs melt.Additionally,the incorporation of Nb element impedes the formation of W-Zr phases,but the introduction of Nb element does not alter the extent of interdiffusion between the constituent elements of the amorphous matrix and W element,indicating that the influence of Nb element on the diffusion of individual elements is minute.

Infiltration,runoff,and slope stability behaviors of infinite slope with macropores based on an improved Green–Ampt model

Infiltration–runoff–slope instability mechanism of macropore slope under heavy rainfall is unclear.This paper studied its instability mechanism with an improved Green–Ampt(GA)model considering the dual-porosity(i.e.,matrix and macropore)and ponding condition,and proposed the infiltration equations,infiltration–runoff coupled model,and safety factor calculation method.Results show that the infiltration processes of macropore slope can be divided into three stages,and the proposed model is rational by a comparative analysis.The wetting front depth of the traditional unsaturated slope is 17.2%larger than that of the macropore slope in the early rainfall stage and 27%smaller than that of the macropore slope in the late rainfall stage.Then,macropores benefit the slope stability in the early rainfall but not in the latter.Macropore flow does not occur initially but becomes pronounced with increasing rainfall duration.The equal depth of the wetting front in the two domains is regarded as the onset criteria of macropore flow.Parameter analysis shows that macropore flow is delayed by increasing proportion of macropore domain(ω_(f)),whereas promoted by increasing ratio of saturated permeability coefficients between the two domains(μ).The increasing trend of ponding depth is sharp at first and then grows slowly.Finally,when rainfall duration is less than 3 h,ωf andμhave no significant effect on the safety factor,whereas it decreases with increasingωf and increases with increasingμunder longer duration(≥3 h).With the increase ofω_(f),the slope maximum instability time advances by 10.5 h,and with the increase ofμ,the slope maximum instability time delays by 3.1 h.

NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation,migration,invasion and cell cycle in vitro

Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer:Integrating Bioinformatics Analysis with Experimental Confirmation

Objective To uncover the mechanisms underlying the development of colorectal cancer(CRC),we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression.Methods We performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on differentially expressed genes(DEGs),constructed a protein-protein interaction(PPI)network to find the top 10 hub genes,and analyzed their expression in colon adenocarcinoma(COAD)and rectum adenocarcinoma(READ).We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting.Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis.Results We found 130 DEGs,with 45 up-regulated and 85 down-regulated in CRC.GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH,zymogen granules,and transmembrane transporter activity.KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion,rheumatoid arthritis,and the IL-17 signaling pathway.We identified 10 hub genes:CXCL1,SLC26A3,CXCL2,MMP7,MMP1,SLC9A2,SLC4A4,CLCA1,CLCA4,and ZG16.GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription.Gene expression analysis revealed that CXCL1,CXCL2,MMP1,and MMP7 were highly expressed in CRC,whereas CLCA1,CLCA4,SLC4A4,SLC9A2,SLC26A3,and ZG16 were expressed at lower levels.Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC.Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines.Importantly,SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation,migration,and invasion.Western blotting analysis revealed that the expression levels of phosphorylated ERK(p-ERK)and phosphorylated JNK(p-JNK)proteins were significantly increased,whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression.Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway.Conclusion Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.