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.

Acute liver failure with thrombotic microangiopathy due to sodium valproate toxicity:A case report

BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly hepatotoxicity.Herein,we report a case of fatal acute liver failure(ALF)with thrombotic microangiopathy(TMA)caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue,severe jaundice accompanied by oliguria,soy sauce-colored urine,and ecchymosis.His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation system.He was diagnosed with drug-induced liver failure combined with TMA.After plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he died.CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.

Clinical and Genetic Characteristics of Alagille Syndrome in Adults

Background and Aims:Alagille syndrome(AGS)is an autosomal dominant multisystem disorder caused by mutations in the JAG1 and NOTCH2 genes.AGS has been rarely reported in adult patients,mainly because its characteristics in adults are subtle.The study aimed to improve the understanding of adult AGS by a descriptive case series.Methods:Eight adults diagnosed with AGS at our hospital between June 2016 and June 2019 were included in the study.Clinical data,biochemical results,imaging results,liver histopathology,and genetic testing were analyzed.Results:Three female and five male patients with a median age of 24.5 years at the time of diagnosis were included in the analysis.The clinical manifestations were adult-onset(62.5%,5/8),cholestasis(50%,4/8),butterfly vertebrae(62.5%,5/8),systolic murmurs(12.5%,1/8),typical facies(12.5%,1/8),posterior embryotoxon,and renal abnormalities(0/8).Genetic sequencing showed that all patients had mutations,with four occurring in the JAG1 gene and four in the NOTCH2 gene.Six were substitution mutations,one was a deletion mutation,and one was a splicing mutation.Five had been previously reported;but the others,one JAG1 mutation and two NOTCH2 mutations were unique and are reported here for the first time.Conclusions:The clinical manifestations highlighted by the current diagnostic criteria for most adults with AGS are atypical.Those who do not meet the criteria but are highly suspicious of having AGS need further evaluation,especially genetic testing.

Abnormal platelet count correlates with poor survival in hepatocellular carcinoma

Background: Normal platelet(PLT) plays a vital role in thrombosis, the inflammatory response, and liver regeneration. The effect of abnormal PLT counts has been seldom explored in hepatocellular carcinoma(HCC); hence, this investigation was conducted to evaluate the prognostic importance of preoperative abnormal PLT count in HCC patients after liver resection retrospectively. Methodology: The PLT counts were determined using Sysmex XT-1800 i automated hematology analyzer and its matching reagents. Patients were divided into two groups: a normal PLT group and an abnormal PLT group. Chi-square test, Kaplan–Meier method, and Cox univariable and multivariable regressions were utilized to analyze the data. Results: A total of 391 HCC patients who underwent liver resection were included in this study. The overall survival(OS) rates were 59% and 31%, and the median survival time was 69 months and 31 months in the normal and abnormal PLT groups, respectively. The PLT level was associated with OS in univariate and multivariate analyses(hazard ratio [HR], 1.991 [95% confidence interval {CI}, 1.412–2.808] and HR, 2.217 [95% CI, 1.556–3.159], respectively). Conclusions: Patients with normal PLT had a better outcome in terms of OS. The results suggested that abnormal PLT count is an independent prognostic factor for HCC patients after liver resection.

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as markers of,and were found to be differentially expressed in,different types of immune cells.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma(2022 version)

Intrahepatic cholangiocarcinoma(iCCA)can originate from the large bile duct group(segment bile ducts and area bile ducts),small bile duct group(septal bile ducts and interlobular bile ducts),and terminal bile duct group(bile ductules and canals of Hering)of the intrahepatic biliary tree,which can be histopathological corresponding to large duct type iCCA,small duct type iCCA and iCCA with ductal plate malformation pattern,and cholangiolocarcinoma,respectively.The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies,tissue structures,growth patterns,invasive behaviors,immunophenotypes,molecular mutations,and surgical prognoses.For these reasons,this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA,mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.