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.

Characterization of the sphingolipid profiling of Emiliania huxleyi against virus infection

Lipidomics approach by UPLC-Q-Exactive-MS was used for the identification,quantification,comparison,and characterization of sphingolipids in virus infected marine Emiliania huxleyi BOF92 cells.The results show that 16 significantly changed sphingolipids(including Cer,CerG1,and SPHm)were identified during viral infection.Our data confirmed previously recognized facts that viral infection led to a shift toward virus-specific sphingolipids,which is consistent with the down-regulation of genes involved in the host de novo sphingolipid biosynthesis.Moreover,we revealed the upregulation of virusencoded homologous genes participating in de novo sphingolipids biosynthesis and virus-specific hydroxylated long chain bases(LCBs)as phytoCer,suggesting the competitive inhibition of host sphingolipid synthesis to produce the required building blocks for viral production,replication,and assembly.Additionally,Cer 40꞉1;2,Cer 40꞉2;2 isomer,and CerG139꞉0;2,Cer 39꞉0;2 as novel metabolite markers might indicate the general dysfunctions in E.huxleyi in response to viral infection.Our results show that viral infection led to a profound remodeling of host sphingolipidome,by which viruses depend on the hijacking of host sphingolipid metabolism to support the viral life cycle.

Obesity-associated steatotic liver exhibits aberrant or altered sphingolipid composition and preferentially accumulates ceramide species containing long chain fatty acids

The sphingolipid (SL) signaling pathways are induced by reactive oxygen species and proin-flammatory molecules, which are shown to be upregulated in the obese state. The present work was conducted to determine if an altered SL pathway exists, and contributes to the pathogenesis of hepatic steatosis associated with obesity. Steatotic and non-steatotic livers were procured from Zucker Obese female rats and their lean counterparts in this pre-clinical study, and assessed for enzymes involved in degradation as well as in phos-phorylation of proapoptotic SLs. The expression of enzymes [sphingo-myelinase (SMase), ceramidase, and sphingosine kinase-1 (SK1)] and apoptotic proteins (Bax and Bcl-2) was quantified by ELISA and by Western Blot. Sphingomyelin (SM), ceramide, ceramide-1 phosphate (C1P), sphingosine (SPH), and sphingosine-1-phosphate (S1P) levels were quantified by high-performance liquid chroma-tography (HPLC)-tandem mass spectroscopy (MS). Obese steatotic livers exhibited significantly upregulated ceramidase and down-regulated SK1 and C1P levels (P < 0.05), as well as significantly lower levels of SM and higher levels of ceramide species containing long chain fatty acids, compared to their lean counterparts. These findings demonstrate that obese liver harbours SLs that favour a proapoptotic environment. Moreover, accumulation of ceramides containing long chain fatty acids could be involved in the pathogenesis of hepatic steatosis.

Sphingolipids in cardiovascular and cerebrovascular systems:Pathological implications and potential therapeutic targets

The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell death.Ceramide and sphingosine usually inhibit proliferation and promote apoptosis,while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis.Because these metabolites are interconvertible,it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate.The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations.A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat,as it not only produces the pro-growth,anti-apoptotic messenger S1P,but also decreases levels of pro-apoptotic ceramide and sphingosine.Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease,and these observations have considerable relevance for future potential therapeutic targets.

Role of sphingosine kinase localization in sphingolipid signaling

The sphingosine kinases, SK1 and SK2, produce the potent signaling lipid sphingosine-1-phosphate (S1P). These enzymes have garnered increasing interest for their roles in tumorigenesis, inflammation, vascular diseases, and immunity, as well as other functions. The sphingosine kinases are considered signaling enzymes by producing S1P, and their activity is acutely regulated by a variety of agonists. However, these enzymes are also key players in the control of sphingolipid metabolism. A variety of sphingolipids, such as sphingosine and the ceramides, are potent signaling molecules in their own right. The role of sphingosine kinases in regulating sphingolipid metabolism is potentially a critical aspect of their signaling function. A central aspect of signaling lipids is that their hydrophobic nature constrains them to membranes. Most enzymes of sphingolipid metabolism, including the enzymes that degrade S1P, are membrane enzymes. Therefore the localization of the sphingosine kinases and S1P is likely to be important in S1P signaling. Sphingosine kinase localization affects sphingolipid signaling in several ways. Translocation of SK1 to theplasma membrane promotes extracellular secretion of S1P. SK1 and SK2 localization to specific sites appears to direct S1P to intracellular protein effectors. SK localization also determines the access of these enzymes to their substrates. This may be an important mechanism for the regulation of ceramide biosynthesis by diverting dihydrosphingosine, a precursor in the ceramide biosynthetic pathway, from the de novo production of ceramide.

Bile acids and sphingolipids in cholangiocarcinoma

Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids(CBAs),which are correlated with bile duct obstruction.

Sphingolipid metabolism affects the anticancer effect of cisplatin

Cisplatin,a DNA crosslinking agent,is widely used for the treatment of a variety of solid tumors.Numerous studies have demonstrated that sphingolipid metabolism,which acts as a target for cisplatin treatment,is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes.Ceramide(Cer),which is the central molecule of this network,has been established to induce apoptosis.However,another molecule,sphingosine-1-phosphate(S1P),exerts the opposite function,i.e.,serves as a regulator of pro-survival.Other sphingolipid molecules,including dihydroceramide,ceramide-1-phosphate,glucosylceramide(Glu Cer),and sphingosine(Sph),or sphingolipid catalytic enzymes such as Sph kinase(Sph K),Cer synthase(Cer S),and S1 P lyase,have also attracted considerable attention,particularly Cer,Glu Cer,Sph K,Cer S,and S1 P lyase,which have been implicated in cisplatin resistance.This review summarizes specific molecules involved in sphingolipid metabolism and related catalytic enzymes affecting the anticancer effect of cisplatin,particularly in relation to induction of apoptosis and drug resistance.

Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

Phosphorylation of the LCB1 subunit of Arabidopsis serine palmitoyltransferase stimulates its activity and modulates sphingolipid biosynthesis

Sphingolipids are the structural components of membrane lipid bilayers and act as signaling molecules in many cellular processes.Serine palmitoyltransferase(SPT)is the first committed and rate-limiting enzyme in the de novo sphingolipids biosynthetic pathway.The core SPT enzyme is a heterodimer consisting of LONG-CHAIN BASE1(LCB1)and LCB2 subunits.SPT activity is inhibited by orosomucoid proteins and stimulated by small subunits of SPT(ssSPTs).However,whether LCB1 is modified and how such modification might regulate SPT activity have to date been unclear.Here,we show that activation of MITOGEN-ACTIVATED PROTEIN KINASE 3(MPK3)and MPK6 by upstream MKK9 and treatment with Flg22(a pathogen-associated molecular pattern)increases SPT activity and induces the accumulation of sphingosine long-chain base t18:0 in Arabidopsis thaliana,with activated MPK3and MPK6 phosphorylating AtLCB1.Phosphorylation of AtLCB1 strengthened its binding with AtLCB2b,promoted its binding with ssSPTs,and stimulated the formation of higher order oligomeric and active SPT complexes.Our findings therefore suggest a novel regulatory mechanism for SPT activity.

Emerging Roles of Sphingolipid Signaling in Plant Response to Biotic and Abiotic Stresses

Plant sphingolipids are not only structural components of the plasma membrane and other endomembrane systems but also act as signaling molecules during biotic and abiotic stresses.However,the roles of sphingolipids in plant signal transduction in response to environmental cues are yet to be investigated in detail. In this review,we discuss the signaling roles of sphingolipid metabolites with a focus on plant sphingolipids.We also mention some microbial sphingolipids that initiate signals during their interaction with plants, because of the limited literatures on their plant analogs.The equilibrium of nonphosphorylated and phosphorylated sphingolipid species determine the destiny of plant cells,whereas molecular connections among the enzymes responsible for this equilibrium in a coordinated signaling network are poorly understood.A mechanistic link between the phytohormone-sphingolipid interplay has also not yet been fully understood and many key participants involved in this complex interaction operating under stress conditions await to be identified.Future research is needed to fill these gaps and to better understand the signal pathways of plant sphingolipids and their interplay with other signals in response to environmental stresses.

Changes of sphingolipids profiles after ischemia-reperfusion injury in the rat liver

Background Hepatic ischemia-reperfusion （I/R） injury occurs in many clinical procedures. The molecular mechanisms responsible for hepatic I/R injury however remain unknown. Sphingolipids, in particular ceramide, play a role in stress and death receptor-induced hepatocellular death, contributing to the progression of several liver diseases including liver I/R injury. In order to further define the role of sphingolipids in hepatic I/R, systemic analysis of sphingolipids after reperfusion is necessary. Methods We investigated the lipidomic changes of sphingolipids in a rat model of warm hepatic I/R injury, by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry （DE MALDI-TOF-MS）. Results The total amounts of ceramide and sphingomyelin and the intensity of most kinds of sphingolipids, mainly sphingomyelin, significantly increased at 1 hour after reperfusion （P 〈0.05） and reached peaks at 6 hours after reperfusion （P 〈0.01） compared to controls. Six new forms of ceramide and sphingomyelins appeared 6 hours after reperfusion, they were （m/z） 537.8, 555.7, 567.7, 583.8, 683.5 and 731.4 respectively. A ceramide-monohexoside （m/z） 804.4 （CMH（d18：1C22：1＋Na）＋） also increased after reperfusion and correlated with extent of liver injury after reperfursion. Conclusions Three main forms of sphingolipids, ceramide, sphingomyelin and ceramide-monohexoside, are related to hepatic I/R injury and provide a new perspective in understanding the mechanisms responsible for hepatic I/R injury.

不同脂质成分影响认知障碍的研究进展

认知障碍是目前主要公共卫生挑战之一,其发病机制尚不明确。目前针对认知障碍尚未发现有效的治疗及干预措施,大部分研究表明通过干预血管危险因素可预防或减缓认知衰退,其中脂质组学成为研究热点。脂质是人体的重要组成部分,其成分可通过不同途径影响认知功能。因此,本文就脂质中常见成分对认知功能的影响做一综述。

Isolation and Functional Characterisation of the Genes Encoding Δ~8-Sphingolipid Desaturase from Brassica rapa

8-Sphingolipid desaturase is the key enzyme that catalyses desaturation at the C8 position of the long-chain base of sphingolipids in higher plants. There have been no previous studies on the genes encoding AS-sphingolipid desaturases in Brassica rapa. In this study, four genes encoding AS-sphingolipid desaturases from B. rapa were isolated and characterised. Phylogenetic analyses indicated that these genes could be divided into two groups： BrD8A, BrD8C and BrD8D in group I, and BrD8B in group II. The two groups of genes diverged before the separation of Arabidopsis and Brassica. Though the four genes shared a high sequence similarity, and their coding desaturases all located in endoplasmic reticulum, they exhibited distinct expression patterns. Heterologous expression in Saccharomyces cerevisiae revealed that BrD8A/B/C/D were functionally diverse AS-sphingolipid desaturases that catalyse different ratios of the two products 8（Z）- and 8（E）-C18-phytosphingenine. The aluminium tolerance of transgenic yeasts expressing BrD8A/B/C/D was enhanced compared with that of control cells. Expression of BrD8A in Arabidopsis changed the ratio of 8（Z）：8（E）-C 18-phytosphingenine in transgenic plants. The information reported here provides new insights into the biochemical functional diversity and evolutionary relationship of AS-sphingolipid desaturase in plants and lays a foundation for further investigation of the mechanism of 8（Z）- and 8（E）-C18- phytosphingenine biosynthesis.

Bile acids and sphingolipids in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

Sphingolipid profiles and their relationship with inflammatory factors in asthmatic patients of different sexes

Background:Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes.This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods:Forty-two asthma patients(27 women and 15 men)admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled.Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry.Sex hormones(estradiol,progesterone,testosterone,and androstenedione)and multiple inflammatory factors(periostin,leptin,IgE,IL-4,IL-5,IL-10,IL-13,IL-17A,and IFN-γ)were also assessed.The eosinophil percentage in induced sputum was also detected.All these data were applied to comparative analysis between sexes.Results:Testosterone was negatively related to periostin(ρ=-0.420,P=0.009)and IL-5(ρ=-0.540,P=0.012),while estradiol was positively related to the blood eosinophil percentage(ρ=0.384,P=0.025).Among the eighteen species of sphingolipids detected in the 42 patients,five ceramide(Cer)species(Cer16:0,Cer:20:0,Cer22:0,Cer24:0,and Cer26:0)and one sphingomyelin(SM)species(SM38:0)were significantly higher in male than in female patients.Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males(ρ=0.943,P=0.005)but negative in females(ρ=-0.561,P=0.030).Conclusions:Testosterone was negatively correlated with eosinophil inflammatory factors,but estradiol was positively correlated.Male asthma patients had higher ceramide and sphingomyelin levels than female patients.Different sexes had opposite correlations with ceramide and IL-5,respectively,suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Sphingolipid metabolism, transport, and functions in plants:Recent progress and future perspectives

Sphingolipids,which comprise membrane systems together with other lipids,are ubiquitous in cellular organisms.They show a high degree of diversity across plant species and vary in their structures,properties,and functions.Benefiting from the development of lipidomic techniques,over 300 plant sphingolipids have been identified.Generally divided into free long-chain bases(LCBs),ceramides,glycosylceramides(GlcCers)and glycosyl inositol phosphoceramides(GIPCs),plant sphingolipids exhibit organized aggregation within lipid membranes to form raft domains with sterols.Accumulating evidence has revealed that sphingolipids obey certain trafficking and distribution rules and confer unique properties to membranes.Functional studies using sphingolipid biosynthetic mutants demonstrate that sphingolipids participate in plant developmental regulation,stimulus sensing,and stress responses.Here,we present an updated metabolism/degradation map and summarize the structures of plant sphingolipids,review recent progress in understanding the functions of sphingolipids in plant development and stress responses,and review sphingolipid distribution and trafficking in plant cells.We also highlight some important challenges and issues that we may face during the process of studying sphingolipids.

Sphingolipid metabolism and drug resistance in ovarian cancer

Despite progress in understanding molecular aberrations that contribute to the development and progression of ovarian cancer,virtually all patients succumb to drug resistant disease at relapse.Emerging data implicate bioactive sphingolipids and regulation of sphingolipid metabolism as components of response to chemotherapy or development of resistance.Increases in cytosolic ceramide induce apoptosis in response to therapy with multiple classes of chemotherapeutic agents.Aberrations in sphingolipid metabolism that accelerate the catabolism of ceramide or that prevent the production and accumulation of ceramide contribute to resistance to standard of care platinum-and taxane-based agents.The aim of this review is to highlight current literature and research investigating the influence of the sphingolipids and enzymes that comprise the sphingosine-1-phosphate pathway on the progression of ovarian cancer.The focus of the review is on the utility of sphingolipid-centric therapeutics as a mechanism to circumvent drug resistance in this tumor type.

Sphingolipids Profiling of Plasma in Patients with Diabetes Mellitus Associated with Atherosclerosis by a Novel Normal-Phase UPLC-QToF MS Method

A novel normal-phase UPLC-QToF MS method was developed for sphingolipids analysis,which was then applied to separate and identify seven classes of sphingolipids in plasma.The time-consuming of this novel method was much shorter than previous 2D LC–MS method,while the sensitivity,repeatability and resolution for sphingolipids analysis were better or comparable.Besides,the differences of lipids in human plasma among diabetes mellitus patients,diabetes mellitus associated with atherosclerosis patients and control subjects were also compared.Finally,12 sphingolipids species were identified as the amounts of which in diabetes mellitus associated with atherosclerosis patients were significantly higher than them in diabetes mellitus patients(VIP>1.0,p value<0.05,fold change>1.5).As the isomers of GalCs and GluCs were successfully separated,it was found that five GluCs,rather than GalCs,were included in these 12 potential biomarkers.These results suggest the need to separate GalCs from GluCs,and also indicated that there may be some extra activation pathways of diabetes mellitus associated with atherosclerosis,different from the atherosclerosis pathway and the diabetes mellitus pathway,causing cardiovascular disease.

miR-139-5p对人肝癌细胞增殖和侵袭的影响

目的 探讨微小RNA(miRNA)-139-5p在肝癌组织中的表达及其对人肝癌细胞增殖、侵袭的影响和潜在的分子机制。方法 采用生物信息学方法,从GEO数据库中下载GSE36915数据集,进行差异miRNA分析,结合TCGA-LICH数据集中的生存数据,筛选与预后显著相关的miRNA。采用实时荧光定量PCR(qRT-PCR)检测miR-139-5p在肝癌及其癌旁组织中的表达。利用CCK-8实验、Transwell实验观察miR-139-5p对人肝癌细胞SK-Hep-1和SMMC-7721的表型变化。采用高通量测序检测过表达miR-139-5p的SK-Hep-1细胞中基因表达的变化,确定miR-139-5p调控的潜在的信号通路和靶基因,并采用免疫印迹实验和报告基因实验进行验证。结果 通过对GSE36915数据集进行分析,共鉴定到50个显著差异表达的miRNA。结合TCGA-LICH数据集中的生存数据,发现在差异最显著的20个miRNA中,miR-15b-3p、miR-1180-3p、miR-139-5p、miR-139-3p与预后显著相关,最终确定miR-139-5p为进一步研究对象。miR-139-5p在100对肝癌组织的相对表达水平显著低于对应癌旁组织[(0.50±0.33) vs (1.02±0.43),P<0.001],且低水平的miR-139-5p肝癌患者中位生存期较短(25.5个月vs 43.0个月,P<0.01)。人肝癌细胞系SK-Hep-1和SMMC-7721中过表达miR-139-5p,可以显著抑制肝癌细胞的增殖和侵袭。高通量测序分析发现,在过表达miR-139-5p的SK-Hep-1细胞中,差异表达基因显著富集在Sphingolipid信号通路。经免疫印迹实验和报告基因实验验证,Sphingolipid信号通路中神经酰胺合成酶6(ceramide synthase 6,CerS6)是miR-139-5p的新的靶点。结论 miR-139-5p在肝癌组织中表达减少,导致其下游靶基因CerS6过量表达,从而激活Sphingolipid信号通路,促进肝癌发生发展。本研究提示miR-139-5p可以作为肝癌治疗的新的靶点。

血清鞘脂联合定量HBsAg对核苷(酸)类似物经治慢性乙型肝炎患者加用聚乙二醇干扰素α后HBsAg阴转的预测价值

目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg阴转的鞘脂标志物。方法该单中心、前瞻性队列研究入组了接受核苷(酸)类似物抗病毒治疗1年以上,HBV-DNA检测不到且HBsAg<1500 IU/mL的HBeAg阴性或已发生HBeAg阴转的CHB患者。入组患者加用peg-IFNα-2a或peg-IFNα-2b抗病毒治疗48周。应用超高效液相色谱-串联质谱方法检测基线、12周、24周血清鞘脂水平。主要研究终点是血清鞘脂对48周HBsAg阴转的预测价值。结果53例CHB患者中有48例完成了48周peg-IFNα联合NAs治疗,其中29.2%(14/48)患者实现了HBsAg阴转。基线、12周、24周血清Cerd18:2/22:0、SMd18:2/26:1在HBsAg阴转组及未阴转组之间存在明显差异(P<0.05)。基线HBsAg低水平(OR(95%CI)=0.993(0.987-0.999),P=0.030)、12周血清SMd18:2/26:1高水平(OR(95%CI)=30.366(1.119-823.914),P=0.043)及24周HBsAg定量下降程度(OR(95%CI)=4.696(1.218-18.062),P=0.025)分别是HBsAg阴转的独立预测因素。基线、12周时血清Cerd18:2/22:0分别联合HBsAg定量较之单独相应随访点HBsAg定量对联合治疗48周时HBsAg阴转的预测价值更高(基线AUC:0.895 vs 0.828;12周AUC:0.893 vs 0.861)。结论血清Cerd18:2/22:0联合HBsAg定量可能是早期预测NAs经治CHB患者加用peg-IFNα治疗48周时HBsAg阴转的良好指标。