Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma

BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.

Role of mi RNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.

Prognostic risk model construction and prognostic biomarkers identification in esophageal adenocarcinoma based on immune-related long noncoding RNA

Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Single-cell landscape analysis reveals distinct regression trajectories and novel prognostic biomarkers in primary neuroblastoma

Neuroblastoma(NB),which is the most common pediatric extracranial solid tumor,varies widely in its clinical presentation and outcome.NB has a unique ability to spontaneously differentiate and regress,suggesting a potential direction for therapeutic intervention.However,the underlying mechanisms of regression remain largely unknown,and more reliable prognostic biomarkers are needed for predicting trajectories for NB.We performed scRNAseq analysis on 17 NB clinical samples and three peritumoral adrenal tissues.Primary NB displayed varied cell constitution,even among tumors of the same pathological subtype.Copy number variation patterns suggested that neuroendocrine cells represent the malignant cell type.Based on the differential expression of sets of related marker genes,a subgroup of neuroendocrine cells was identified and projected to differentiate into a subcluster of benign fibroblasts with highly expressed CCL2 and ZFP36,supporting a progressive pathway of spontaneous NB regression.We also identified prognostic markers(STMN2,TUBA1A,PAGE5,and ETV1)by evaluating intra-tumoral heterogeneity.Lastly,we determined that ITGB1 in M2-like macrophages was associated with favorable prognosis and may serve as a potential diagnostic marker and therapeutic target.In conclusion,our findings reveal novel mechanisms underlying regression and potential prognostic markers and therapeutic targets of NB.

A pan-cancer analysis identifies SOAT1 as an immunological and prognostic biomarker

Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.

m7G Methylation-Related Gene NUDT10 as novel prognostic biomarker and its ceRNA regulatory network in colorectal cancer

Background:Colorectal cancer(CRC)is a life-threatening malignant disease of the digestive system,which is still a leading cause of cancer death worldwide.RNA methylation,a fundamental process in epigenetic regulation,also plays an important role in tumor development.Nevertheless,the functional mechanisms of 7-methylguanosine(m7G)methylation-related gene in CRC are unclear.Methods:The differential expression of m7G methylation-related gene between CRC tissues and normal tissues in UCSC XENA,TCGA and GTEx was verified using R.Cox regression,Nomogram were used to construct corresponding prognostic models of CRC.Kaplan-Meier analysis,receiver operating characteristic curve analysis,clinical correlation analysis and enrichment analysis were used to further investigate the correlation and functional mechanisms of m7G methylation-related gene with CRC.Immuno-infiltration was used to verify the relationship between nudix hydroxylase 10(NUDT10)and immune cells,while methylation analysis was used to study the promoter methylation of NUDT10.Immunohistochemistry was used to analyze the protein expression between CRC tissues and normal tissues.The ceRNA regulatory network was used to identify the mRNA-miRNA-lncRNA regulatory axis.Results:The m7G methylation-related gene NUDT10 was lowly expressed in CRC.Cox regression,Nomogram and calibration curve finally identified NUDT10 as the novel prognostic biomarker of CRC and constructed the corresponding prognostic models.The results of immunohistochemistry showed that the protein expression levels of NUDT10 differed between CRC tissues and normal tissues.In addition,NUDT10 had predictive power for CRC and the expression of NUDT10 in CRC was closely associated with immune infiltration.Gene Ontology,Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis revealed that biological functions such as the regulation of angiogenesis,muscle contraction,transporter complex and gated channel activity,pathways such as heme metabolism,hypoxia,cholinergic synapse,apical junction and epithelial mesenchymal transition all play a role in the development of CRC.The study of methylation revealed that NUDT10 showed hyper-methylation in both CRC and normal tissues,in which the promoter methylation of DNA in CRC was lower than that in normal colon and rectum.The ceRNA regulatory network revealed that 3 lncRNAs such as XIST,interfered the expression of NUDT10 through 6 miRNAs such as hsa-miR-23a-3p,and then affected the development of CRC.Conclusion:The m7G methylation-related gene NUDT10 can be used as novel biomarker in CRC.A total of 3 lncRNAs,including XIST,are involved in the expression of NUDT10 in CRC through 6 miRNAs such as hsa-miR-23a-3p.

Blood microRNAs as potential diagnostic and prognostic markers in cerebral ischemic injury

MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.

Development and validation of a tumor microenvironment-related prognostic signature in lung adenocarcinoma and immune infiltration analysis

Objective Tumor-infiltrating immune cells and stromal cells in the tumor microenvironment(TME)significantly affect the prognosis of and immune response to lung adenocarcinoma(LUAD).In this study,we aimed to develop a novel TME-related prognostic model based on immune and stromal genes in LUAD.Methods LUAD data from the TCGA database were used as the training cohort,and three Gene Expression Omnibus(GEO)datasets were used as the testing cohort.The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm was used to analyze the immune and stromal genes involved in the TME.Kaplan-Meier and Cox regression analyses were used to identify prognostic genes and construct a TME-related prognostic model.Gene set enrichment analysis and TIMER were used to analyze the immune features and signaling pathways of the model.Results A TME-related prognostic model based on six hub genes was generated that significantly stratified patients into the high-and low-risk groups in terms of overall survival.The model had strong predictive ability in both the training(TCGA)and testing(GEO)datasets and could serve as an independent prognostic factor for LUAD.Moreover,the low-risk group was characterized by greater immune cell infiltration and antitumor immune activity than the high-risk group.Importantly,the signature was closely associated with immune checkpoint molecules,which may serve as a predictor of patient response to immunotherapy.Finally,the hub genes BTK,CD28,INHA,PIK3CG,TLR4,and VEGFD were considered novel prognostic biomarkers for LUAD and were significantly correlated with immune cells.Conclusion The TME-related prognostic model could effectively predict the prognosis and reflect the TME status of LUAD.These six hub genes provided novel insights into the development of new therapeutic strategies.

Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

BACKGROUND The carcinogenesis of colorectal cancer(CRC)involves many different molecules and multiple pathways,and the specific mechanism has not been elucidated until now.Existing studies on the proteomic signature profiles of CRC are relatively limited.Therefore,we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues.AIM To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC.METHODS Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021.Data independent acquisition(DIA)quantitative proteomic analysis was performed using high-performance liquid chromatography–mass spectrometry/mass spectrometry(nano-UHPLC–MS/MS)to identify differen tially expressed proteins,among which those with a P adj value(t test,BH correction)<0.05 and an absolute fold change(|log2FC|)>2 were identified as potential markers.Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays,and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC.RESULTS Significantly differential protein expression was observed between cancer tissues and normal tissues.Compared with normal tissues,1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj<0.05 and|log2FC|>2,and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis,including ribosome biogenesis in eukaryotes,focal adhesion,extracellular matrix-receptor interactions and other tumor metabolism processes.Moreover,cyclin-dependent kinase inhibitor 2A(CDKN2A)expression was markedly upregulated in CRC,as validated by immunohistochemistry(0.228 vs 0.364,P=0.0044),and was significantly enriched in tumor proliferation and signal transduction pathways such as the cell cycle and p53 signaling pathways.High CDKN2A expression was significantly correlated with poor prognosis(P=0.021).These results demonstrated that CDKN2A functions as a driver of CRC.CONCLUSION Our study provides a comprehensive proteomic signature of CRC and highlights CDKN2A as a potential powerful prognostic marker and precision therapeutic target.

Prognostic tumor microenvironment gene and the relationship with immune infiltration characteristics in metastatic breast cancer

The aim of this study was to reveal genes associated with breast cancer metastasis,to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment,and to screen for prognostic biomarkers.Gene expression data of breast cancer patients and their metastases were downloaded from the GEO,TCGA database.R language package was used to screen for differentially expressed genes,enrichment analysis of genes,PPI network construction,and also to elucidate key genes for diagnostic and prognostic survival.Spearman’s r correlation was used to analyze the correlation between key genes and infiltrating immune cells.We screened 25 hub genes,FN1,CLEC5A,ATP8B4,TLR7,LY86,PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues.However,patients with higher expression of CD1C,IL-18 breast cancer had a better prognosis in the 10 years survival period,while patients with high expression of FN1,EIF4EBP1 tumors had a worse prognosis.In addition,TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis.In this study,gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8^(+)T lymphocytes,while GSE43816,GSE62327 and TCGA databases showed that CD8^(+)T lymphocytes were closely associated with breast cancer progression.Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.

Recognition of prognostic biomarker and its association with immune infiltrates in breast cancer associated with inflammation

Objective:To identify prognostic biomarkers in breast cancer(BRCA)associated with inflammation.Materials andmethods:WGCNA was used to identify prognostic biomarkers in BRCA based on TCGA-BRCA and GSE70947 datasets.GO and KEGG exploration was made to analyze the specific mechanisms of interest genes.Results:There were 9 modules in TCGA-BRCA and 19 modules in the GSE70947 constructed and 639 overlapping genes extracted.There were ten genes recognized as hub genes,SAA1 and CXCL2 were identified as key genes.Furthermore,we found that SAA1 and CXCL2 were positively related to the levels of tumor-infiltrating immune cells in BRCA with TIMER.Conclusions:SAA1 and CXCL2 is highly correlated with BRCA and its prognosis was greatly related to TIICs.

ABCC8 is correlated with immune cell infiltration and overall survival in lower grade glioma

ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.

Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression

Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and diseases.Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression.This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins.In the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC.Moreover,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.

CIB1 as a Potential Diagnosis and Prognosis Biomarker in Uveal Melanoma

Background: Uveal melanoma (UVM) is the most common primary intraocular tumor in adults. However, identification of the effective biomarker for the diagnosis and treatment of UVM remains to be explored. Calcium and integrin-binding protein 1 (CIB1) is emerging as an important factor in tumor progression. Purpose: To determine the contribution of CIB1 in the diagnosis of UVM. Method: Immunohistochemical staining is used to detect the CIB1 expression level, while Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN online tools were used to analyze patient survival and CIB1 correlation genes in UVM. Integrative analysis using STRING and GeneMANIA predicted the correlated genes with CIB1 in UVM. Results: CIB1 expression level in UVM was significantly enhanced when compared with that in paracancerous tissues. A higher CIB1 expression level resulted in a significantly worse disease-free survival as well as overall survival. Moreover, the survival probability of patients was associated with body weight and gender of the patients with UVM. The correlated genes with CIB1 in UVM, and the similarity of the genes in UVM expression and survival heatmap were verified. Furthermore, Gene ontology enrichment analysis revealed that CIB1 and its correlated genes are significantly enriched in ITGA2B-ITGB3-CIB1 complex, regulation of intracellular protein transport and regulation of ion transport. Conclusions: Our novel findings suggested that CIB1 might be a potential diagnostic predictor for UVM, and might contribute to the potential strategy for UVM treatment by targeting CIB1.

Gastrointestinal microbiota:A predictor of COVID-19 severity?

Coronavirus disease 2019(COVID-19),caused by a severe acute respiratory syndrome coronavirus 2 infection,has raised serious concerns worldwide over the past 3 years.The severity and clinical course of COVID-19 depends on many factors(e.g.,associated comorbidities,age,etc)and may have various clinical and imaging findings,which raises management concerns.Gut microbiota composition is known to influence respiratory disease,and respiratory viral infection can also influence gut microbiota.Gut and lung microbiota and their relationship(gut-lung axis)can act as modulators of inflammation.Modulating the intestinal microbiota,by improving its composition and diversity through nutraceutical agents,can have a positive impact in the prophylaxis/treatment of COVID-19.

Poly-hydroxylated bile acids and their prognostic roles in Alagille syndrome

Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.Methods Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.A good prognosis was defined as survival with native liver and total bilirubin(TB)<85.5 μmol/L,while a poor prognosis was defined as either liver transplantation,death from liver failure,or TB ≥ 85.5 μmol/L at the last follow-up.Results We found that the concentrations of two poly-hydroxylated bile acids,tauro-2β,3α,7α,12α-tetrahydroxylated bile acid(THBA)and glyco-hyocholic acid(GHCA),were significantly increased in patients with good prognosis compared to those with poor prognosis[area under curve(AUC)=0.836 and 0.782,respectively]in the discovery cohort.The same trend was also observed in the molar ratios of GHCA to glyco-chenodeoxycholic acid(GCDCA)and tetrahydroxylated bile acid(THCA)to tauro-chenodeoxycholic acid(TCDCA)(both AUC=0.836).A validation cohort confirmed these findings.Notably,tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00%(92.31%sensitivity and 83.33%specificity);GHCA at>607.69 nmol/L was associated with native liver survival[hazard ratio:13.03,95%confidence interval(CI):(2.662-63.753),P=0.002].Conclusions We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients.Enhanced hydroxylation of bile acids may result in better clinical outcomes.

The more the messier：centrosome amplification as a novel biomarker for personalized treatment of colorectal cancers

Colon cancer is currently the third most common cancer and second most fatal cancer in the United States,resulting in approximately 600,000 deaths annually.Though colorectal cancer death rates are decreasing by about 3%every year,disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis,the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments.Colon carcinogenesis is notably a slow process that can take decades.Known factors that contribute to the development of colon cancer are mutational,epigenetic and environmental,and risk factors include age,history of polyps and family history of colon cancer.Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability,microscopic satellite instability,or CpG island methylator phenotype.In this review,we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology.Moreover,the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients.Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.