Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.

Lipid metabolism-related long noncoding RNAs:A potential prognostic biomarker for hepatocellular carcinoma

The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.

Identification prognostic features related to sphingolipid metabolism and experimental validation of TRIM47 in hepatocellular carcinoma

Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

Objective The activities and products of carbohydrate metabolism are involved in key processes of cancer.However,its relationship with hepatocellular carcinoma(HCC)is unclear.Methods The cancer genome atlas(TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases.Differentially expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk score.Next,gene set enrichment analysis(GSEA)was performed on the risk model genes.The sensitivity of the risk model to immunotherapy and chemotherapy was also explored.Results A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2,ACYP1,OGDHL,ACADS,and TKTL1,were identified.Moreover,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC patients.Both the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy sensitivity.Furthermore,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy sensitivity.Eventually,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy drugs.The results of the experiments in HCC tissue samples validated the expression of the risk model genes.Conclusion Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.

Prognostic model and treatment plan analysis of hepatocellular carcinoma based on genes related to glutamine metabolism

Objective:To identify the prognosis of hepatocellular carcinoma(HCC)and the effect of anti-cancer drug therapy by screening glutamine metabolism-related signature genes because glutamine metabolism plays an important role in tumor development.Methods:We obtained gene expression samples of normal liver tissue and hepatocellular carcinoma from the TCGA database and GEO database,screened for differentially expressed glutamine metabolismrelated genes(GMRGs),constructed a prognostic model by lasso regression and step cox analysis,and assessed the differences in drug sensitivity between high-and low-risk groups.Results:We screened 23 differentially expressed GMRGs by differential analysis,and correlation loop plots and PPI protein interaction networks indicated that these differential genes were strongly correlated.The four most characterized genes(CAD,PPAT,PYCR3,and SLC7A11)were obtained by lasso regression and step cox,and a risk model was constructed and confirmed to have reliable predictive power in the TCGA dataset and GEO dataset.Finally,immunotherapy is better in the high-risk group than in the low-risk group,and chemotherapy and targeted drug therapy are better in the low-risk group than in the high-risk group.Conclusion:In conclusion,we have developed a reliable prognostic risk model characterized by glutamine metabolism-related genes,which may provide a viable basis for the prognosis and Treatment options of HCC patients.

Molecular imaging and therapy targeting coppermetabolism in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC.Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells.Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis.Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans.Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography(PET)using radioactive copper as a tracer.It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer,suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake.In addition to copper modulation therapy with copper chelators,short-interference RNA specific for human copper transporter 1(h Ctr1)may be used to suppress growth of HCC by blocking increased copper uptake mediated by h Ctr1.Furthermore,altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides.Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.

Low glucose metabolism in hepatocellular carcinoma with GPC3 expression

AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transporter 1(GLUT1),and whole-body ^(18)F-FDG PET/c T for measuring tumour glucose uptake were performed in 55 newly diagnosed Hcc patients.The maximum standard uptake value(s UVmax)and tumour-to-non-tumourous liver uptake(T/NT)ratio were used to quantify ^(18)F-FDG uptake.In vitro ^(18)F-FDG uptake assay of GPc3-expressing Hep G2 and non-GPc3-expressing RH7777 cel ls was used to examine the effect of GPc3 in cellular glucose metabolism.The relationships between GPc3 expression and ^(18)F-FDG uptake,GLUT1 expression,tumour differentiation,and other clinical indicators were analysed using spearman rank correlation,univariateand multiple logistic regression analyses.RESULTSPositive GPc3 expression was observed in 67.3%of Hcc patients,including 75.0%of those with well or moderately differentiated Hcc and 36.4%of those with poorly differentiated Hcc.There was an inverse relationship between GPc3 expression and s UVmax(Spearman correlation coefficient=-0.281,P=0.038)and a positive relationship between GLUT1 expression and sU Vmax(Spearman correlation coefficient=0.681,P<0.001)in patients with Hcc.Univariate analysis showed that two glucose metabolic parameters(sU Vmax and T/NT ratio),tumour differentiation,lymph node metastasis,and TNM stage were all significantly associated with GPc3 expression(P<0.05),whereas GLUT1 expression,sex,age,tumour size,intrahepatic lesion number,and distant metastasis showed no statistical association(P>0.05).Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with Hcc(P<0.05).In vitro assay revealed that the uptake of ^(18)F-FDG in GPc3-expressing HepG2 cells was significantly lower than that of non-GPc3-expressing RH7777 cells(t=-20.352,P<0.001).CONCLUSIONThe present study demonstrated that GPc3 expression is inversely associated with glucose metabolism,suggesting that GPc3 may play a role in regulating glucose metabolism in Hcc.

The impact of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with hepatocellular carcinoma after radical resection

Background:Metabolic dysfunction-associated fatty liver disease(MAFLD)is recently proposed an entity by a group of international experts.However,the impact of MAFLD on the prognosis of patients with hepatocellular carcinoma(HCC)is not clear.The aim of this study was to explore the influence of MAFLD for the prognosis of HCC after radical resection.Methods:HCC patients who received radical resection were enrolled.The recurrence-free survival(RFS)and overall survival(OS)were compared between MAFLD and non-MAFLD.Results:A total of 576 HCC patients were included,and among them 114(19.8%)met the diagnostic criteria of MAFLD.The median RFS was 34.0 months in the MAFLD group and 19.0 months in the non-MAFLD group.The 1-,3-,and 5-year RFS rates were 64.9%,49.1%and 36.1%in the MAFLD group,which were higher than those of the non-MAFLD group(59.4%,35.3%and 26.5%,respectively,P=0.01).The mean OS was 57.0 months in the MAFLD group and 52.2 months in the non-MAFLD group.There was no statistical difference in OS rate between the MAFLD group and non-MAFLD group.Similar results were found in HBV-related HCC patients in the subgroup analysis.Univariate analysis revealed that MAFLD was a protective factor for RFS in HCC patients after radical resection(P<0.05),and there was no association between MAFLD and OS rate(P>0.05).Multivariate analysis demonstrated that MAFLD was not an independent protective factor for HCC patients with radical resection.Conclusions:MAFLD improves RFS rate in HCC patients with radical resection,but is not an independent protective factor and not associated with OS rate.

Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma

AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G genes.METHODS Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) and controls(n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0and SNPstats were utilized for statistical analysis. RESULTS Showed that age ≥ 46 years(OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking(OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years(OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit(OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298 C in codominant model(OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model(OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model(OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756 G in the additive model(OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66 G in the codominant model(OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model(OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model(OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756 G in the additive model(OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G(OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms. CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756 G, MTHFR A1298 C and MTRR A66 G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756 G polymorphism are associated with cirrhosis.

IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF CYTOCHROME P-450HSjISOZYME, AN ENZYME RELATED TO NITROSAMINE METABOLISM, IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA

Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.

Hepatocellular carcinoma in patients with metabolic dysfunctionassociated fatty liver disease: Can we stratify at-risk populations?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a new nomenclature recently proposed by a panel of international experts so that the entity is defined based on positive criteria and linked to pathogenesis,replacing the traditional non-alcoholic fatty liver disease(NAFLD),a definition based on exclusion criteria.NAFLD/MAFLD is currently the most common form of chronic liver disease worldwide and is a growing risk factor for development of hepatocellular carcinoma(HCC).It is estimated than 25%of the global population have NAFLD and is projected to increase in the next years.Major Scientific Societies agree that surveillance for HCC should be indicated in patients with NAFLD/MAFLD and cirrhosis but differ in non-cirrhotic patients(including those with advanced fibrosis).Several studies have shown that the annual incidence rate of HCC in NAFLD-cirrhosis is greater than 1%,thus surveillance for HCC is costeffective.Risk factors that increase HCC incidence in these patients are male gender,older age,presence of diabetes and any degree of alcohol consumption.In non-cirrhotic patients,the incidence of HCC is much lower and variable,being a great challenge to stratify the risk of HCC in this group.Furthermore,large epidemiological studies based on the general population have shown that diabetes and obesity significantly increase risk of HCC.Some genetic variants may also play a role modifying the HCC occurrence among patients with NAFLD.The purpose of this review is to discuss the epidemiology,clinical and genetic risk factors that may influence the risk of HCC in NAFLD/MAFLD patients and propose screening strategy to translate into better patient care.

Investigation of Calcitonin and Calcitonin Gene-related Peptide in 88 Cases of Medullary Thyroid Carcinoma

Objective： To investigate the changes of calcitonin （CT） and calcitonin gene-related peptide （CGRP） in patients with medullary thyroid carcinoma （MTC）. Methods： Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. The immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP in 30 newly diagnosed MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy. Results： （1） The rate of residual tumor had a significant difference between the normal serum CT group one month after operation and the elevated group at the same period （P〈0.01）. （2） Immunohistochemical study revealed the positive rate of CT was about 98%, and that of the CGRP was 87.8%. （3） Part of the patients had an elevated CGRP levels while CT levels was normal. （4） The serum CT levels were decreased to a stable range one week after operation. Conclusion： CT is a useful index to evaluate the efficacy of surgical treatment. The measurement of serum CGRP is helpful in the diagnosis of MTC, especially for those whose preoperative CT levels are normal.

Do medullary thyroid carcinoma patients with high calcitonin require bilateral neck lymph node clearance?A case report

BACKGROUND In clinical work,85%-90%of malignant thyroid diseases are papillary thyroid cancer(PTC);thus,clinicians neglect other types of thyroid cancer,such as medullary thyroid carcinoma(MTC).CASE SUMMARY We report a 53-year-old female patient with a preoperative calcitonin level of 345 pg/mL.There was no definitive diagnosis of MTC by preoperative fine-needle aspiration cytology or intraoperative frozen pathology,but the presence of PTC and MTC was confirmed by postoperative paraffin pathology.The patient underwent total thyroidectomy and bilateral central lymph node dissection.Close follow-up at 1.5 years after surgery revealed no signs of recurrence or metastasis.CONCLUSION The issue in clinical work-up regarding types of thyroid cancer provides a novel and challenging idea for the surgical treatment of MTC.In the absence of central lymph node metastasis,it is worth addressing whether patients with high calcitonin can undergo total thyroidectomy and bilateral central lymph node dissection without bilateral lateral neck lymph node dissection.

A Case of Medullary Thyroid Carcinoma Combined with Papillary Microcarcinoma and Literature Review

Background: The histologic type of thyroid carcinomas includes follicular, papillary carcinomas, and medullary carcinomas. The reports about the histological, immunohistochemical, and ultrastructural characteristics of each kind of thyroid carcinomas were common, but the simultaneous occurrence of a medullary and papillary carcinoma as 2 distinct tumors has been reported extremely rarely. Objects: To explore the pathogenesis, clinicopathological characteristics, immunohistochemical phenotype, and pathological diagnosis of medullary thyroid carcinoma combined with papillary thyroid microcarcinoma. Methods: The clinicopathological characteristics and immunohistochemical phenotype of a patient with left medullary thyroid carcinoma combined with right papillary thyroid microcarcinoma were retrospectively studied. Then, relevant literature was thus reviewed. Results: General appearance: The size of the left thyroid lobe was 2.5 × 2 × 1 cm, the cut surface was gray and red, and a nodule with a diameter of 1.3 cm could be observed. The cut surface of the nodule was gray and yellow, solid, and hard. The size of the right lobe of the thyroid gland was 0.7 × 0.6 × 0.5 cm, and a gray nodule with a diameter of 0.4 cm was seen on the cut surface. The cut surface of the nodule was gray, solid, and hard. Observation under the microscope: the left nodular tumor cells were round, oval, or plasma cell-like, some areas were arranged in nests, and some areas were arranged in beams. Calcification and sheet-like eosinophilic amyloid deposits could be seen in the stroma. The nodule on the right showed a branched papillary structure, the covering cells on the surface of the nipple were ground glass-like nuclei, and nuclear grooves and pseudo-inclusion bodies in the nucleus could be observed. Immunohistochemistry: left lobe tumor cells Calcitonin, CEA, TTF-1, CD56, CgA, and Syn are all (+), CK19 and TG were both (&#8722;);right lobe tumor cells CK19 and TG are both (+), Calcitonin, CD56, CgA, and Syn are all (&#8722;). Conclusions: The origin, clinicopathological manifestations, and immunophenotypes of medullary thyroid carcinoma and papillary thyroid carcinoma are different. It is relatively rare for the two to occur at the same time. The diagnosis mainly depends on the microscopic morphology and immunophenotype characteristics.