Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.

Promoter methylation of Wnt/β-Catenin signal inhibitor TMEM88 is associated with unfavorable prognosis of nonsmall cell lung cancer

Objective:Recent research has indicated that altered promoter methylation of oncogenes and tumor suppressor genes is an important mechanism in lung cancer development and progression.In this study,we investigated the association between promoter methylation of TMEM88,a possible inhibitor of the Wnt/β-Catenin signaling,and the survival of patients with nonsmall cell lung cancer(NSCLC).Methods:Twelve pairs of tumor and adjacent non-tumor samples were used for microarray analyses of DNA methylation and gene expression.For validation,more than two hundred additional samples were analyzed for methylation using bisulfite pyrosequencing and for gene expression using q RT-PCR.Then the cell function were tested by wound healing,transwell,CCK8 and cell cycle assay.Results:Our analysis of patient specimens showed that TMEM88 methylation was higher in NSCLC tumors(82.2%±10.3,P<0.01)compared with the adjacent normal tissues(65.9%±7.2).The survival analysis revealed that patients with high TMEM88methylation had a shorter overall survival(46 months)compared with patients with low TMEM88 methylation(>56 months;P=0.021).In addition,we found that demethylation treatment could inhibit tumor cell proliferation,migration,and invasion,which was supportive of an association between methylation and survival.Conclusions:Based on these consistent observations,we concluded that TMEM88 may play an important role in NSCLC progression and that promoter methylation of TMEM88 may serve as a biomarker for NSCLC prognosis and treatment.

Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

Objective MicroRNA plays a vital role in gene expression,and microRNA dysregulation is involved in carcinogenesis.The miR- 196a-2 polymorphism rsll614913 is reportedly associated with cancer susceptibility.This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rsll614913 polymorphism. Results A significant association was found between rsll614913 polymorphism and cancer risk in four genetic models(CT vs.TT, OR=1.15,95%CI=1.05-1.27;CC vs.TT,OR=1.23,95%CI=1.08-1.39;Dominant model,OR=1.17,95%CI=1.06-1.30;Additive model, OR=1.08,95%CI=1.01-1.14).In the subgroup analysis of different tumor types,the C allele was associated with increased risk of lung, breast,and colorectal cancer,but not with liver,gastric,or esophageal cancer.In the subgroup analysis by ethnicity,a significantly increased risk of cancer was found among Asians in all genetic models,but no associations were found in the Caucasian subgroup. Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility,especially lung cancer,colorectal cancer,and breast cancer among Asian populations.

Re-evaluation of ABO gene polymorphisms detected in a genomewide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population

Pancreatic cancer is a fatal malignancy with an increasing incidence in Shanghai, China. A genomewide association study(GWAS) and other work have shown that ABO alleles are associated with pancreatic cancer risk. We conducted a population-based case-control study involving 256 patients with pathologically confirmed pancreatic ductal adenocarcinoma(PDAC) and 548 healthy controls in Shanghai, China, to assess the relationships between GWAS-identified ABO alleles and risk of PDAC. Carriers of the C allele of rs505922 had an increased cancer risk [adjusted odds ratio(OR) = 1.42, 95% confidence interval(CI): 1.02-1.98] compared to TT carriers. The T alleles of rs495828 and rs657152 were also significantly associated with an elevated cancer risk(adjusted OR = 1.58, 95% CI: 1.17-2.14; adjusted OR = 1.51, 95% CI: 1.09-2.10). The rs630014 variant was not associated with risk. We did not find any significant gene-environment interaction with cancer risk using a multifactor dimensionality reduction(MDR) method. Haplotype analysis also showed that the haplotype CTTC was associated with an increased risk of PDAC(adjusted OR = 1.46, 95% CI: 1.12-1.91) compared with haplotype TGGT. GWAS-identified ABO variants are thus also associated with risk of PDAC in the Chinese population.

Pu-erh tea: A review of a healthful brew

Pu-erh tea has been used for thousands of years to treat metabolic diseases.Recognized in Shen Nong's Herbal Classic,a compendium kept by the first traditional Chinese practitioners,it is still highly valued for its hypocholesterolemic and hypolipidemic effects.This review reports the processing and bioactive components of pu-erh tea.Recent human and animal studies of pu-erh tea and its potential therapeutic mechanisms have also been summarized.The interaction of liver and gut microbiome regulates the puerh tea biotransformation and endogenous metabolism,and thus contributes to the health benefits.

Parent and friend influences on the multiple health behavior of Pacific Islander adolescents

Youth obesity has increased dramatically in the United States, disproportionally affecting Hawaiian populations. The primary research objective was to describe the influence of parent and friends on the dietary, physical activity, and sedentary behaviors of Pacific Islander high school students. Data were collected from classrooms within a private high school on the Hawaiian island Oahu. Participants were Pacific Islander adolescents attending a high school in Hawaii. Participating adolescents completed a questionnaire, followed by a corresponding focus group;specifically reporting the social-level influences on their dietary and activity behaviors. Adolescents then interviewed their parent/guardian, asking questions relative to their perceived health-related influence. Participating adolescents (N = 60) were 53% female with a mean age of 16.93 (SD = 0.63), and their parents/guardians (N = 47) were 75% female with a mean age of 46.72 (SD = 5.11). Outcomes revealed parents/ guardians as the dominant influence on adolescents’ dietary behaviors, and time spent with parents was almost exclusively sedentary. In comparison, adolescents were more active with friends, but shared less healthy dietary habits. Results provide groundwork for similar examinations and culturally tailored interventions among similar adolescent populations.

Hepatitis B Virus Screening Patterns amongst Physicians in Hawaii: Changes in a Decade

Purpose: Hawaii had the highest incidence of liver cancer in the US and had a unique patient population with many immigrants from the Pacific and Asia where Hepatitis B virus (HBV) was endemic. HBV screening in high risk populations was a recommended measure of preventative medicine, thus we sought to examine physician screening patterns for HBV in Hawaii. Methods: We retrospectively analyzed billing claims from 1999 to 2009 from the largest healthcare coverage provider in the state of Hawaii. We identified all patients (>18 years) who underwent HBV screening based on Current Procedural Terminology (CPT) billing codes. We collected data on age, gender and specialty of physicians ordering the screening tests. Analysis was done in 2013 and 2014. Results: Of an estimated 700,000 covered lives, 125,576 patients underwent HBV screening. We stratified the patients into two eras from 1999-2004 (N = 52,245) and 2005-2009 (N = 73,331) to examine temporal trends. In the first era, 30,975 women (59.3%) underwent HBV screening, compared to 49,950 women (69.1%) screened in the 2005-2009 era. There absolute number of tests increased, but the proportion done by primary care MDs decreased from 55.6% to 44.9%. OB/GYN screened 15.6% in the early era and 26.9% in later era. Conclusions: There was an increase in women aged 18 - 40 years screened in the 2005-2009 era compared to 1999-2004, most likely due to OB/GYN physicians’ screening of prenatal women. Physician education on HBV vaccination/treatment or appropriate referral should include OB/GYN as well as primary care physicians.

Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children

AIMTo identify metabolic signatures in urine samples from healthy and inflammatory bowel disease(IBD)children.METHODSWe applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry(MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year(baseline,6 and 12 mo),and 27age-and gender-matched healthy children.RESULTSurinary metabolic profiles of IBD children differ significantly from healthy controls.Such metabolic differences encompass central energy metabolism,amino acids,bile acids and gut microbial metabolites.In particular,levels of pyroglutamic acid,glutamic acid,glycine and cysteine,were significantly higher in IBD children in the course of the study.This suggests that glutathione cannot be optimally synthesized and replenished.Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known,we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions.CONCLUSIONThe present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status.

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid

Liver injury caused by acetaminophen(AP)overdose is a leading public health problem.Although APinduced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone(NAPQI),a toxic metabolite of AP,resulting in cell damage,emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota.However,the gut microbiota-involved mechanism remains largely unknown.In our study,we found that vancomycin(Vac)pretreatment(100 mg/kg,twice a day for 4 days)attenuated AP-induced liver injury,altered the composition of gut microbiota,and changed serum metabolic profile.Moreover,we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid(2-HB),which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels.Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies

Cancer cells are usually characterized by hyperactive glucose metabolism,which can often lead to glucose scarcity;thus,alternative pathways to rewire cancer metabolism are required.Here,we demonstrated that GLUT3 was highly expressed in colorectal cancer(CRC)and negatively linked to CRC patient outcomes,whereas GLUT1 was not associated with CRC prognosis.Under glucoselimiting conditions,GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis.Notably,GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress.Mechanistically,low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway.Furthermore,high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens.Together,the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.

Alpha-fetoprotein testing for hepatocellular carcinoma may not be helpful in nonalcoholic steatohepatitis

Background & Objectives: Diagnosing hepatocellular carcinoma (HCC) often utilizes serum tumor markers. Although the most commonly used tumor marker in clinical practice, alpha-fetoprotein (AFP) is not included in recent guidelines for diagnosing HCC. The overall performance characteristics of AFP as a tumor marker is viewed as insufficiently sensitive or specific. The diagnostic value of AFP specifically in nonalcoholic steatohepatitis (NASH) related HCC is unknown. We aimed to determine the utility of AFP testing in NASH-related HCC. Methods: Retrospective review of 737 HCC patients referred from 1993- 2011 to a single facility treating the majority of chronic liver disease in Hawaii. HCC was diagnosed histologically by percutaneous biopsy, liver biopsy at the time of surgery, or examination of the resected liver. Patients were classified according to HCC risk factors including NASH, hepatitis B and C infection, and alcohol-related. Other data collected included: demographics, ethnicity, presence of cirrhosis, tumor characteristics (size, number, vascular invasion), diabetes, hyperlipidemia, body mass index (BMI) and blood testing to calculate Model for End-Stage Liver Disease (MELD) score. Elevated AFP was defined as >20 ng/mL. Sensitivity of AFP was determined and compared between various subgroups. Results: Elevated AFP levels were detected in 64.3% of patients. AFP sensitivity was 47% for NASH-related HCC (n = 100), and 67.2% for HCC with viral or alcoholic risk factors (n = 637) (OR 0.43, 95% CI 0.28 - 0.66, p = 0.0001). Elevated AFP had higher sensitivity in females (71.9% vs. 61.8%, OR 1.58, 95% CI 1.1 - 2.27, p = 0.013), non-diabetics (67.4% vs. 57.2%, OR 0.65, 95% CI 0.47 - 0.89, p = 0.0093), and cirrhotics (67.1% vs. 56.8%, OR 1.55, 95% CI 1.10 - 2.19, p = 0.0012).AFP did not vary significantly with regard to hyperlipidemia or BMI. AFP was more sensitive in advanced disease including tumors > 5 cm, multiple tumors, or vascular invasion (all with p < 0.05). AFP did not vary with MELD score. Conclusions: Normal AFP is common in NASH-related HCC. Better tumor markers may be needed to optimally screen and diagnose NASH-related HCC. Without more effective tumor markers, HCC detection relies heavily upon imaging and liver biopsy.

Novel strategy for disease risk prediction incorporating predicted gene expression and DNA methylation data:a multi-phased study of prostate cancer

Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative method.Methods:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy.In the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best performance.Using an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual scores.Furthermore,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls.Results:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family history.The overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family history.Conclusions:We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa.Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.

A new mission for an old anti-cancer drug:harnessing hepatocyte-specific metabolic pathways against liver tumors

In a recent study published in Nature Cancer,Shi et al.reported the identification of the small molecule YC-1 as the selective drug against primary liver tumor cells due to the specific expression of sulfotransferase family 1A member 1(SULT1A1)in hepatocytelineage cells.1 This study offered new insights into repurposing an old anti-cancer drug via harnessing hepatocyte-specific metabolic enzymes to treat primary liver tumors.

Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and mouse HCC.The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival.The roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by AAV9.Prior to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor load.The treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body weight.Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing.Within the tumors,silencing Gal1 inhibited translational initiation,elongation,and termination.Furthermore,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas CD8-dependent.Overall,Gal1 silencing has a promising potential for HCC treatment.

Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma

Colorectal cancer(CRC)and hepatocellular carcinoma(HCC)are the second and third most common causes of death by cancer,respectively.The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol,smoking,diet,obesity and diabetes.Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC.However,the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors.In this review,we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC.Based on the idea that the gut microbiota are an additional“lifeline”and contribute to the tumor microenvironment,we can observe from previously published literature how the microbiota can cause a shift in the balance from normal→inflammation→diminished inflammation from early to later disease stages.This pattern leads to the hypothesis that tumor survival depends on a less proinflammatory tumor microenvironment.The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.

Phytochemistry,Metabolism, and Metabolomics of Ginseng

Ginseng, as a medicinal plant, has been used for thousands of years in China, Korea, and Japan, and the study on ginseng is a hotspot in the research field as evidenced by about 7000 scientific papers in PUBMED. In recent decades, many ginseng studies focused on the metabolism and metabolomics of ginseng or its active ingredients using modern bioanalytical technologies. To date, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. In the past decades, rapid development of analytical technologies has facilitated the advancement of ginseng research in many ways. In this review, we focus on the advances of ginseng research in chemistry, pharmacology, and metabolomics. We also provide the comments on the significance as well as challenges of metabolomics-based ginseng studies.

Clinical and molecular sub-classification ofhepatocellular carcinoma relative to alpha-fetoproteinlevel in an Asia-Pacific island cohort

Aim: Increased serum alpha-fetoprotein (AFP) levels are associated with specific molecular subclasses of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC. Methods: Whole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis. Results: Statistically confident (false discovery rate < 0.05) sub-classifications were made in 98% (39/40) of tumors. Patient sub-groups differed significantly with regards to serum AFP level, with significantly lower levels in the S3 sub-group as compared to S1 (P = 0.048) and S2 (P = 0.010). Serum AFP > 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival. Conclusion: Distinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

BRCA相关蛋白1在恶性间皮瘤中的表达缺失及其在鉴别诊断中的应用价值

目的探讨BRCA相关蛋白1（BRCA assoeiated protein1，BAP1）在恶性间皮瘤、肺腺癌、肺鳞癌和癌肉瘤中表达情况及其在鉴别诊断中的作用。方法选取恶性间皮瘤22例，其中上皮样型17例，肉瘤样型2例，双相型3例。另选取侵犯胸膜的非小细胞肺癌共80例（肺腺癌40例、肺鳞癌40例）和全身各部位癌肉瘤15例作为对照。应用免疫组织化学方法检测BAP1在各组病例的表达情况，并分析各组表达差异。同时所有病例均检测了常规用于间皮瘤鉴别诊断的抗体组合，包括calretinin、wTl、细胞角蛋白5／6、D2．40、CAM5．2、癌胚抗原、甲状腺转录因子1、Napsin A、p63和p40。结果所有80例非小细胞肺癌和15例癌肉瘤均BAP1核表达阳性，而64％（14／22）恶性间皮瘤出现BAP1表达缺失，两者差异有统计学意义（P〈0．01）。间皮瘤诊断标志物组合中，增加BAP1后，诊断恶性间皮瘤的诊断正确度达93％。BAP1灶性表达表明肿瘤细胞具有多克隆性。结论BAP1核表达缺失有助于鉴别恶性间皮瘤和非小细胞肺癌。因此推荐BAP1与其他间皮瘤抗体一起应用于恶性间皮瘤的诊断，提高恶性间皮瘤的诊断准确性。