Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expr...Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO) and analyzed to obtain differentially expressed genes(DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. The key gene was determined using R language, STRING, and Cytoscape, and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas(TCGA) and quantitative real-time PCR(q RT-PCR) for BRCA tissues of 37 patients. The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis(GSEA).Results Of 10 hub genes seleceed from 302 DEGS, UBE2C was identified as the gene associated with BRCA survival. The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and q RT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy. UBE2C may be an potential immune-related prognostic biomarker for BRCA.展开更多
AIM: To evaluate the utility of the innovative fecal tumor M2-Pyruvate kinase (M2-PK) test in our daily clinical routine, as a marker for the pre-selection of patients who should subsequently undergo colonoscopy for t...AIM: To evaluate the utility of the innovative fecal tumor M2-Pyruvate kinase (M2-PK) test in our daily clinical routine, as a marker for the pre-selection of patients who should subsequently undergo colonoscopy for the diagnosis or exclusion of colorectal cancer. METHODS: Fecal tumor M2-PK was measured in stool samples of 96 study participants (33 patients with colorectal cancer, 21 patients with rectal carcinoma and 42 controls) who all underwent total colonoscopy. RESULTS: In 39 of 42 individuals in the control group, fecal tumor M2-PK was below 4.0 kU/L (93% specificity). Colorectal tumors were accompanied by a highly significant increase (P < 0.001) in fecal tumor M2- PK levels (median: colon carcinoma, 23.1 kU/L; rectal carcinoma, 6.9 kU/L; colorectal carcinoma, 14.7 kU/L), which correlated with Duke’s staging and T-classification. The overall sensitivity was 78% for colorectal cancer, increasing from 60% for stage T1 to 100% for stage T4 and from 60% for Duke’s A to 90% for Duke’s D tumors. CONCLUSION: Fecal tumor M2-PK is an appropriately sensitive tool to pre-select those patients requiring colonoscopy for the further diagnostic confirmation or exclusion of colorectal cancer.展开更多
The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatm...The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatment is available for advanced cancers, which remain a major cause of morbidity and mortality. Clearly, there is urgent need to unravel novel biomarkers for early detection. Most of the functional information of the cancer-associated genes resides in the proteome. The later is an exceptionally complex biological system involving several proteins that function through posttranslational modifications and dynamic inter-molecular collisions with partners. These protein complexes can be regulated by signals emanating from cancer cells, their sur-rounding tissue microenvironment, and/or from the host. Some proteins are secreted and/or cleaved into the extracellular milieu and may represent valuable serum biomarkers for diagnosis purpose. It is estimated that the cancer proteome may include over 1.5 million proteins as a result of posttranslational processing and modifications. Such complexity clearly highlights the need for ultra-high resolution proteomic technology for robust quantitative protein measurements and data acquisition. This review is to update the current research efforts in high-resolution proteomic technology for discovery and monitoring cancer biomarkers.展开更多
Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in indiv...Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in individual patients. Optimised clinical management of compensated chronic liver diseases requires precise definition of the stage of liver fibrosis, the main determinant of prognosis and of most therapeutic decisions. Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Direct markers are based on biochemical parameters directly linked to fibrogenesis while indirect markers use simple or more sophisticated parameters that correlate with liver fibrosis stages. Non-invasive markers of liver fibrosis have been tested in different forms of chronic liver disease and showed variable diagnostic performance, but accuracy rarely was above 75%-80%. Better results were obtained when markers were combined. On this line, we have recently proposed a set of algorithms that combine sequentially indirect non-invasive markers of liver fibrosis, reaching 90%-95% diagnostic accuracy with significant reduction in the need for liver biopsy. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy.展开更多
AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagno...Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.展开更多
The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenes...The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.展开更多
The ecological environment in the East China Sea(ECS)and the Yellow Sea(YS)has changed significantly due to sea-level rising and the Kuroshio incursion since the last deglaciation.In this study,biomarker records of co...The ecological environment in the East China Sea(ECS)and the Yellow Sea(YS)has changed significantly due to sea-level rising and the Kuroshio incursion since the last deglaciation.In this study,biomarker records of core F10B from the mud area southwest off Cheju Island(MSWCI)were generated to evaluate phytoplankton productivity and community structure changes in response to environmental evolution during the last 14 kyr.The contents of diatom,dinoflagellate and haptophyte biomarkers(brassicasterol,dinosterol and C37alkenones)display similar trends,with increasing phytoplankton productivity during the last 14kyr due to the increased influences of the Kuroshio,and especially due to the eddy-induced upwelling during the late Holocene.On the other hand,the contents of terrestrial biomarkers(C28+C30+C32n-alkanols)and terrestrial organic matter(TOM)proxies(TMBR′and BIT)all reveal decreasing TOM input into the area around the sampling site for the 14 kyr,mostly due to sea-level ris-ing.Phytoplankton biomarker ratios reveal a shift from a haptophyte-dominated community at 6.2 2.5 kyr BP to a diatom-dominated community at 2.5 1.45 kyr BP,likely caused by a stronger cold eddy circulation system at 2.5 1.45 kyr BP in the MSWCI.展开更多
Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This...Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-likereceptors (TLR) 2 and 4, and β-defensin-1. Further-more, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/ plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and mul-tiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.展开更多
Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that asses...Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate(GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine(SCr) and cystatin C(Cys C). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associationswith disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 m L/min per 1.73 m2. Equations combining Cys C and SCr perform better than the equations using either Cys C or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, Cys C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.展开更多
Background Heart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiogra...Background Heart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a rela-tively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction (pEF) and compared its performance with that of B-type natriuretic peptide (BNP). Methods Thirty-five pEF patients with HF (HFpEF group) and 43 pEF patients without HF (control group) were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, pre dictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared. Results Levels of galec- tin-3 and BNP were 23.09 ±6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant (P 〈 0.01). As a bio- marker for HF diagnosis in study subjects, galectin-3 showed sensitivity and specificity of 94.3% and 65.1%, respectively, at a cutoff value of 17.8 ug/mL. BNP showed sensitivity and specificity of 77.1% and 90.7%, respectively, at a cutoff value of 100 pg/mL. Galectin-3 was a significantly more sensitive (P 〈 0.05) but less specific (P 〈 0.01) biomarker compared with BNP. Differences in positive predictive value, negative predictive value, and accuracy between galectin-3 and BNP markers were not significant (P 〉 0.05). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.891 (0.808-0.974) and 0.896 (0.809-0.984) for galectin-3 and BNP, respec- tively, with no significant difference between the two values (P 〉 0.05). Conclusions The level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.展开更多
文摘Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO) and analyzed to obtain differentially expressed genes(DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. The key gene was determined using R language, STRING, and Cytoscape, and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas(TCGA) and quantitative real-time PCR(q RT-PCR) for BRCA tissues of 37 patients. The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis(GSEA).Results Of 10 hub genes seleceed from 302 DEGS, UBE2C was identified as the gene associated with BRCA survival. The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and q RT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy. UBE2C may be an potential immune-related prognostic biomarker for BRCA.
文摘AIM: To evaluate the utility of the innovative fecal tumor M2-Pyruvate kinase (M2-PK) test in our daily clinical routine, as a marker for the pre-selection of patients who should subsequently undergo colonoscopy for the diagnosis or exclusion of colorectal cancer. METHODS: Fecal tumor M2-PK was measured in stool samples of 96 study participants (33 patients with colorectal cancer, 21 patients with rectal carcinoma and 42 controls) who all underwent total colonoscopy. RESULTS: In 39 of 42 individuals in the control group, fecal tumor M2-PK was below 4.0 kU/L (93% specificity). Colorectal tumors were accompanied by a highly significant increase (P < 0.001) in fecal tumor M2- PK levels (median: colon carcinoma, 23.1 kU/L; rectal carcinoma, 6.9 kU/L; colorectal carcinoma, 14.7 kU/L), which correlated with Duke’s staging and T-classification. The overall sensitivity was 78% for colorectal cancer, increasing from 60% for stage T1 to 100% for stage T4 and from 60% for Duke’s A to 90% for Duke’s D tumors. CONCLUSION: Fecal tumor M2-PK is an appropriately sensitive tool to pre-select those patients requiring colonoscopy for the further diagnostic confirmation or exclusion of colorectal cancer.
基金Project supported by the National Cancer Institute of Canada
文摘The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatment is available for advanced cancers, which remain a major cause of morbidity and mortality. Clearly, there is urgent need to unravel novel biomarkers for early detection. Most of the functional information of the cancer-associated genes resides in the proteome. The later is an exceptionally complex biological system involving several proteins that function through posttranslational modifications and dynamic inter-molecular collisions with partners. These protein complexes can be regulated by signals emanating from cancer cells, their sur-rounding tissue microenvironment, and/or from the host. Some proteins are secreted and/or cleaved into the extracellular milieu and may represent valuable serum biomarkers for diagnosis purpose. It is estimated that the cancer proteome may include over 1.5 million proteins as a result of posttranslational processing and modifications. Such complexity clearly highlights the need for ultra-high resolution proteomic technology for robust quantitative protein measurements and data acquisition. This review is to update the current research efforts in high-resolution proteomic technology for discovery and monitoring cancer biomarkers.
文摘Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in individual patients. Optimised clinical management of compensated chronic liver diseases requires precise definition of the stage of liver fibrosis, the main determinant of prognosis and of most therapeutic decisions. Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Direct markers are based on biochemical parameters directly linked to fibrogenesis while indirect markers use simple or more sophisticated parameters that correlate with liver fibrosis stages. Non-invasive markers of liver fibrosis have been tested in different forms of chronic liver disease and showed variable diagnostic performance, but accuracy rarely was above 75%-80%. Better results were obtained when markers were combined. On this line, we have recently proposed a set of algorithms that combine sequentially indirect non-invasive markers of liver fibrosis, reaching 90%-95% diagnostic accuracy with significant reduction in the need for liver biopsy. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy.
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
基金Project (No. 985-2-015-24) partly supported by "985" Project of Research Grants from Peking University, China
文摘Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.
文摘The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.
基金supported by the National Basic Research Program of China (973 Program 2010CB428901)the National Natural Science Foundation of China (Grant Nos.41020164005,41221004)the ‘111’ Project
文摘The ecological environment in the East China Sea(ECS)and the Yellow Sea(YS)has changed significantly due to sea-level rising and the Kuroshio incursion since the last deglaciation.In this study,biomarker records of core F10B from the mud area southwest off Cheju Island(MSWCI)were generated to evaluate phytoplankton productivity and community structure changes in response to environmental evolution during the last 14 kyr.The contents of diatom,dinoflagellate and haptophyte biomarkers(brassicasterol,dinosterol and C37alkenones)display similar trends,with increasing phytoplankton productivity during the last 14kyr due to the increased influences of the Kuroshio,and especially due to the eddy-induced upwelling during the late Holocene.On the other hand,the contents of terrestrial biomarkers(C28+C30+C32n-alkanols)and terrestrial organic matter(TOM)proxies(TMBR′and BIT)all reveal decreasing TOM input into the area around the sampling site for the 14 kyr,mostly due to sea-level ris-ing.Phytoplankton biomarker ratios reveal a shift from a haptophyte-dominated community at 6.2 2.5 kyr BP to a diatom-dominated community at 2.5 1.45 kyr BP,likely caused by a stronger cold eddy circulation system at 2.5 1.45 kyr BP in the MSWCI.
基金Broad Medical Research Program, No. IBD-0119RNIH/NIDDK grant, No. 5R21DK77064+1 种基金NIH/NIDDK, No. KO1-DK62264NIH Ruth L. Kirschstein National Research Service Awards, Proctor & Gamble Investigator Initiated Grants
文摘Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-likereceptors (TLR) 2 and 4, and β-defensin-1. Further-more, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/ plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and mul-tiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.
文摘Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate(GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine(SCr) and cystatin C(Cys C). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associationswith disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 m L/min per 1.73 m2. Equations combining Cys C and SCr perform better than the equations using either Cys C or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, Cys C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.
文摘Background Heart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a rela-tively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction (pEF) and compared its performance with that of B-type natriuretic peptide (BNP). Methods Thirty-five pEF patients with HF (HFpEF group) and 43 pEF patients without HF (control group) were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, pre dictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared. Results Levels of galec- tin-3 and BNP were 23.09 ±6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant (P 〈 0.01). As a bio- marker for HF diagnosis in study subjects, galectin-3 showed sensitivity and specificity of 94.3% and 65.1%, respectively, at a cutoff value of 17.8 ug/mL. BNP showed sensitivity and specificity of 77.1% and 90.7%, respectively, at a cutoff value of 100 pg/mL. Galectin-3 was a significantly more sensitive (P 〈 0.05) but less specific (P 〈 0.01) biomarker compared with BNP. Differences in positive predictive value, negative predictive value, and accuracy between galectin-3 and BNP markers were not significant (P 〉 0.05). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.891 (0.808-0.974) and 0.896 (0.809-0.984) for galectin-3 and BNP, respec- tively, with no significant difference between the two values (P 〉 0.05). Conclusions The level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.