Serum Biomarkers For Detection Research Articles

Novel serum biomarkers for detection of excessive alcohol use.

Construct interview that correctly identifies those with alcohol use disorder have limitation, especially when the subjects are motivated to minimize the magnitude of drinking behavior. Current laboratory tests to detect excessive alcohol consumption are limited by marginal sensitivity/specificity. Excessive drinking has been shown to affect several organ systems, which may be reflected in changes in quantity of plasma proteins. Our aim was to employ novel proteomic analyses to identify potential markers for excessive alcohol use. A prospective case-control study included 49 controls and 54 excessive drinkers (discovery cohort). The serum proteomic analyses in these subjects were performed, and the results were tested in the verification cohort (40 controls and 40 excessive drinkers). Using the appropriate cutoff and confirmation with ELISA, we identified 4 proteins which were significantly elevated in the serum of excessive drinkers: AT-rich interactive domain-containing protein 4B (ARID4B), phosphatidylcholine-sterol acyltransferase (LCAT), hepatocyte growth factor-like protein (MST1), and ADP-ribosylation factor 6 (ARL6). The performance of the conventional markers (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [GGT], percentage of carbohydrate-deficient transferrin [%CDT], and mean corpuscular volume [MCV]) discriminating between excessive alcohol use and controls had an area under the curve (AUC) ranging from 0.21 (ALT) to 0.67 (MCV). The AUC of these novel proteins showed the improvement in the detection of excessive drinkers compared to conventional laboratory tests, ranging from 0.73 (for ARID4B) to 0.86 (for ARL6). We have identified 4 novel proteins that can discern subjects with excessive alcohol use. Further studies are needed to determine the clinical implications of these markers to detect excessive alcohol use and confirm abstinence.

Assessment of Serum Hydroxyproline and Osteopontin as Noninvasive Markers of Hepatic Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection is a progressive disease that may result in chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Liver fibrosis is an essential factor that must be considered in the management of patients with HCV. Although liver biopsy represents the gold standard for evaluating the presence, type and stage of liver fibrosis, this technique remains a costly and invasive procedure. Therefore, several diagnostic methods for determining liver fibrosis, such as the detection of serum biomarkers, have been used. Objective: To evaluate the use of serum hydroxyproline (HYP) and osteopontin (OPN) as non invasive direct markers to assess the degree of hepatic fibrosis in Egyptian patients with chronic HCV infection in comparison to indirect markers such as aspartate aminotransferase platelet ratio index (APRI) and to determine the most diagnostically accurate non invasive marker of hepatic fibrosis, hoping to replace liver biopsy in the next few years. Methodology: This study was carried out on 48 patients with chronic HCV infection who had undergone liver biopsy and scored as mild fibrosis (F1), moderate fibrosis (F2), sever fibrosis (F3) and liver cirrhosis (F4) based on Metavir scoring system, and 12 age and sex matched controls. The serum levels of HYP and OPN were measured by enzyme linked immunosorbent assay (ELISA). Results: There was a highly significant increase in HYP, OPN and APRI in all patients groups in comparison to control group and their increase was significantly associated with the degree of hepatic fibrosis. Furthermore, HYP, OPN and APRI values showed highly significant increase in significant hepatic fibrosis (F2- F4) in comparison to mild fibrosis (F1), and in hepatic cirrhosis (F4) in comparison to hepatic fibrosis (F1-F3). There was a highly significant positive correlation between serum HYP level, OPN and APRI. The receiver operating characteristic (ROC) curve analysis revealed that OPN has the highest area under the curve (AUC) value for discriminating fibrosis stages, followed by HYP and lastly APRI. Conclusion: This study demonstrated that OPN was the most diagnostically accurate marker for assessing the severity of hepatic fibrosis and served as a prognostic index towards the progression of hepatic fibrosis to cirrhosis in patients with chronic HCV infection, followed by HYP and lastly APRI. These findings indicated that OPN and HYP could be used as non invasive markers of hepatic fibrosis and cirrhosis which would help to reduce the need for liver biopsy in chronic HCV infection

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens (TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.

Human serum biomarker detection based on a cascade signal amplification strategy by a DNA molecule machine.

A convenient method is presented that employs a DNA machine for protein biomarker detection. The detection limit is 400 times lower compared to the method without a DNA machine. This study provides a promising method that could realize most protein biomarker detections without the corresponding aptamers, using a DNA machine for signal amplification.

Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor.

Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10(-16) g ml(-1) in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10(-4).

The Degree of Global DNA Hypomethylation in Peripheral Blood Correlates with That in Matched Tumor Tissues in Several Neoplasia

There are no good blood and serum biomarkers for detection, follow up, or prognosis of brain tumors. However, they are needed for more detailed tumor classification, better prognosis estimation and selection of an efficient therapeutic strategy. The aim of this study was to use the epigenetic changes in DNA of peripheral blood samples as a molecular marker to diagnose brain tumors as well as other diseases. We have applied a very precise thin-layer chromatography (TLC) analysis of the global amount of 5-methylcytosine (m5C) in DNA from brain tumors, colon and breast cancer tissues and peripheral blood samples of the same patients. The m5C level in tissue DNA from different brain tumor types, expressed as R coefficient, changes within the range of 0.2–1.6 and overlaps with R of that of blood samples. It negatively correlates with the WHO malignancy grade. The global DNA hypomethylation quantitative measure in blood, demonstrates a big potential for development of non-invasive applications for detection of a low and a high grade brain tumors. We have also used this approach to analyze patients with breast and colon cancers. In all these cases the m5C amount in DNA cancer tissue match with data of blood. This study is the first to demonstrate the potential role of global m5C content in blood DNA for early detection of brain tumors and others diseases. So, genomic DNA hypomethylation is a promising marker for prognosis of various neoplasms as well as other pathologies.

Secretome-Based Identification of TFPI2, A Novel Serum Biomarker for Detection of Ovarian Clear Cell Adenocarcinoma

Of all of the epithelial ovarian cancers (EOC), clear cell adenocarcinoma (CCA) has the worst clinical prognosis. Furthermore, the conventional EOC biomarker CA125 is more often negative in CCA than in other subtypes of EOC. This study sought to discover a new diagnostic biomarker that would allow more reliable detection of CCA. Using mass spectrometry, we compared proteins in conditioned media from cell lines derived from CCA and other types of EOC. We identified 30 extracellular or released proteins specifically present in CCA-derived cell lines. Bioinformatics analyses identified a serine protease inhibitor, tissue factor pathway inhibitor 2 (TFPI2), as a potential biomarker for CCA. Real time RT-PCR and Western blot analyses revealed that TFPI2 was exclusively expressed in CCA-derived cell lines and tissues. For clinical validation, we measured levels of TFPI2 and CA125 in a set of sera from 30 healthy women, 30 patients with endometriosis, and 50 patients with CCA, using an automated enzyme-linked immunosorbent assay systems. Serum levels of TFPI2 were significantly elevated in CCA patients, even those with normal CA125 levels. In terms of area under the receiver operating characteristic curve (AUC), TFPI2 was superior to CA125 in discriminating CCA patients from healthy women (AUC 0.97 for TFPI2 versus AUC 0.80 for CA125), or from patients with endometriosis (AUC 0.93 for TFPI2 versus 0.80 for CA125). This is the first evidence for TFPI2 as a serum biomarker of CCA. We propose that this biomarker may be useful for detection of CCA and for monitoring the transformation from endometriosis into CCA.

Multiplexed immunoassay biosensor for the detection of serum biomarkers — β-HCG and AFP of Down Syndrome based on photoluminescent water-soluble CdSe/ZnS quantum dots

A multiplexed immunoassay biosensor for detecting serum biomarkers was developed by using photoluminescent (PL) aqueous CdSe/ZnS quantum dots (QDs) with high efficiency and stability as fluorescence labels and carboxyl functionalized microporous nylon membrane as a matrix. Two main biomarkers of Down Syndrome (DS), β-human chorionic gonadotrophin (β-HCG) and α-fetal protein (AFP), were selected for detection in this biosensor system. For specific detection of DS, antibody-immobilized microporous nylon membrane first captured the targeted antigens from the physiological samples and formed immunocomplexes (antibody–antigen) on the membrane surface. Then the immunocomplexes continued to react with QDs conjugated antibodies (labeled antibodies), and formed triplex “sandwich” structure, which was confirmed by AFM and confocal microscopy. Quantitative detection of β-HCG and AFP was also realized, the detectable level of this new biosensor was as low as 1×10−6IU/L for β-HCG and 1ng/mL for AFP in a relatively short assay time without any enrichment.

Lung cancer screening: from imaging to biomarker

Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.

New Insights Into the Pathogenesis of Ovarian Carcinoma

Recent discoveries about the pathogenesis of ovarian cancer have suggested that it can no longer be thought of as a single entity, but that the histologically defined ovarian cancer subtypes are different diseases, with different precursor lesions and distinct biomarker expression profiles. Most serous carcinomas probably arise from the fallopian tube. Clear cell and endometrioid carcinomas are associated with endometriosis and likely originate from ectopic endometrium. The focus of large ovarian cancer screening trials has been detection of macroscopic ovarian abnormalities by ultrasonography and detection of serum biomarkers associated with the most common (serous) subtype of ovarian cancer. The only completed and phase three randomized controlled trial failed to achieve the objective of reducing ovarian cancer mortality and was not able to demonstrate a stage migration effect of the screening. Future screening strategies have to incorporate our growing understanding of each subtype of pelvic (ovarian or fallopian tube) cancer, its organ of origin, and disease-specific biomarkers. We review how our current understanding of pathogenesis should prompt a reexamination of data from ovarian cancer screening studies and discuss potential designs for future screening strategies.

On-chip dual detection of cancer biomarkers directly in serum based on self-assembled magnetic bead patterns and quantum dots

A sandwich immunoassay method for rapid detection of dual cancer biomarkers in serum on a magnetic field controllable microfluidic chip (MFCM-Chip) was established. A nickel pattern was used to generate high magnetic field gradients to increase the magnetic force on the superparamagnetic beads (SPMBs), which enabled the rapid generation of controllable SPMB patterns in microfluidic channels. The SPMB patterns could keep stable during the fast continuous washing process even at a flow rate of 50μL/min. This approach demonstrated excellent specificity because the fast continuous washing could remove non-specifically adsorptive contaminants more efficiently than fixed volume batch washing. This approach was used to simultaneously detect carcinoma embryonic antigen (CEA) and α-fetoprotein (AFP) directly in serums. The whole on-chip detection was finished within 40min, which was much faster than conventional enzyme-linked immunosorbent assay (ELISA) method. High luminescent streptavidin modified QDs (SA-QDs) were used as fluorescence indicators, and the detection limits were 3.5ng/mL and 3.9ng/mL for CEA and AFP, respectively. The linear ranges were from 10.0ng/mL to 800.0ng/mL. With the high sensitivity, high selectivity and short assay time, this approach could be used for rapid, high throughput detection of cancer biomarkers in clinical trials.

Multiplexed detection of cardiac biomarkers in serum with nanowire arrays using readout ASIC

Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications.

The use of fluorescence correlation spectroscopy (FCS) as an alternative biomarker detection technique: a preliminary study

Biomarkers are essential part of daily medical practice. Currently, biomarkers are being used both for diagnostic and prognostic purposes. There are many approaches e.g. ELISA by which biomarker levels are detected from patient samples. However, all these approaches are laborious, time consuming and expensive. There is therefore a general need for exploring new technique which can overcome these drawbacks. Here, we present a preliminary study for detection of serum biomarkers by fluorescence correlation spectroscopy (FCS) based diagnostic technique. FCS is a technique basically used for spatial and temporal analysis of molecular interactions of extremely low-concentration biomolecules in solution. FCS is able to measure diffusion time of the fluorescent molecules passing through the open detection volume and it can also measure the average number of fluorescent molecules passing through the detection volume. Because diffusion speed is correlated with shape and molecular mass of the fluorescent molecule, this property makes it possible to study the complex formation between a small fluorescently labelled and a large unlabelled molecule. In this preliminary study, we utilize this FCS property for detection of serum biomarker. Further studies on various pathological serum samples are warranted to explore further aspects of this technique.

Solution-phase detection of dual microRNA biomarkers in serum

A strategy for the simultaneous detection of multiple microRNA (miRNA) targets was developed utilizing fluorophore/quencher-labeled oligonucleotide probe sets. Two miRNA targets (miR-155 and miR-103), whose misregulation has afforded them status as putative biomarkers in certain types of cancer, were detected using our assay design. In the absence of target, the complementary fluorophore-probe and quencher-probe hybridize, resulting in a fluorescence resonance energy transfer-based quenching of the fluorescence signal. In the presence of unlabeled target, however, the antisense quencher-probe can hybridize with the target, resulting in increased fluorescence intensity as the quencher-probe is sequestered beyond the Förster radius of the fluorescent-probe. The assay design was tested in multiple matrices of buffer, cellular extract, and serum; and detection limits were found to be matrix-dependent, ranging from 0.34 to 8.89 pmol (3.4-59.3 nM) for miR-155 and 2.90-11.8 pmol (19.3-79.0 nM) for miR-103. Single, double, and triple nucleotide selectivity was also tested. Additionally, miR-155 concentrations were assessed in serum samples obtained directly from breast cancer patients without the need for RNA extraction. This assay is quantitative, possesses a low detection limit, can be applied in multiple complex matrices, and can obtain single-nucleotide selectivity. This method can be employed for the multiplex detection of solution-phase DNA or RNA targets and, more specifically, for the direct detection of serum miRNA biomarkers.

Early diagnosis of sepsis using serum biomarkers

Sepsis, an innate immunological response of systemic inflammation to infection, is a growing problem worldwide with a relatively high mortality rate. Immediate treatment is required, necessitating quick, early and accurate diagnosis. Rapid molecular-based tests have been developed to address this need, but still suffer some disadvantages. The most commonly studied biomarkers of sepsis are reviewed for their current uses and diagnostic accuracies, including C-reactive protein, procalcitonin, serum amyloid A, mannan and IFN-γ-inducible protein 10, as well as other potentially useful biomarkers. A singular ideal biomarker has not yet been identified; an alternative approach is to shift research focus to determine the diagnostic relevancy of multiple biomarkers when used in concert. Challenges facing biomarker research, including lack of methodology standardization and assays with better detection limits, are discussed. The ongoing efforts in the development of a multiplex point-of-care testing kit, enabling quick and reliable detection of serum biomarkers, may have great potential for early diagnosis of sepsis.

Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

IntroductionDetection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients.MethodsWe used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available.ResultsThe presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence and increased time to metastasis.ConclusionsAutoantibodies to specific cancer associated glycoforms of MUC1 are found more frequently and at higher levels in early stage breast cancer patients than in women with benign breast disease or healthy women. Association of strong antibody response with reduced rate and delay in metastases suggests that autoantibodies can affect disease progression.

Soluble E‐cadherin as a serum biomarker candidate: Elevated levels in patients with late‐stage colorectal carcinoma and FAP

Various strategies have been tested to identify serum biomarkers in patients with cancer. Recently, the entire of proteins released by cultured tumor cells into the media, the so-called secretome, has been suggested as a promising source for biomarker discovery. Ectodomains of membrane proteins cleaved from the cell surface represent a surprisingly abundant and apparently stable subset of this subproteome. Aiming for the detection of serum biomarkers for patients with colorectal cancer (CRC), we have previously detected significant amounts of the soluble form of E-cadherin in the secretomes of CRC cells. Here, we report a comprehensive analysis of sE-cadherin levels in sera from patients with CRC, colorectal adenoma, inflammatory bowel disease and familial adenomatous polyposis (FAP). Whereas mean sE-cadherin levels in patients with inflammatory bowel disease (mean: 4.7 μg/ml, SD: 1.5 μg/ml), with adenomas (mean: 4.6 μg/ml, SD: 3.0 μg/ml) and early stage cancers (mean: 4.9 μg/ml, SD: 4.7 μg/ml) do not significantly differ from healthy controls (mean: 4.8 μg/ml, SD: 1.9 μg/ml), patients with Stage III and Stage IV carcinomas display a significant increase (mean: 6.1 μg/ml, SD: 2.6 μg/ml). In individual patients with late-stage CRC, sE-cadherin serum levels directly reflect their disease status over time. These findings suggest a potential application of sE-cadherin as an alternative diagnostic biomarker for monitoring disease particularly in patients with carcinoembryonic antigen negative tumors. In patients with FAP, on the other hand, we also detected a significant increase of serum sE-cadherin levels (mean: 5.8 μg/ml, SD: 2.8 μg/ml), but this was regardless of their tumor load and colectomy status.

New serum biomarkers for detection of tuberculosis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

New technologies for the early detection of tuberculosis (TB) are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. The aim of the present study was to screen for the potential protein biomarkers in serum for the diagnosis of TB using proteomic fingerprint technology. Proteomic fingerprint technology combining protein chips with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to profile the serum proteins from 50 patients with TB, 25 patients with lung disease other than TB, and 25 healthy volunteers. The protein fingerprint expression of all the serum samples and the resulting profiles between TB and control groups were analyzed with the Biomarker Wizard system. A total of 30 discriminating m/z peaks were detected that were related to TB (p<0.01). The model of biomarkers constructed by the Biomarker Patterns Software based on the three biomarkers (2024, 8007, and 8598 Da) generated excellent separation between the TB and control groups. The sensitivity was 84.0% and the specificity was 86.0%. Blind test data indicated a sensitivity of 80.0% and a specificity of 84.2%. The data suggested a potential application of SELDI-TOF MS as an effective technology to profile serum proteome, and with pattern analysis, a diagnostic model comprising three potential biomarkers was indicated to differentiate people with TB and healthy controls rapidly and precisely.

Serum Level of Fibrinogen A.ALPHA. Chain Fragment Increases in Chronic Thromboembolic Pulmonary Hypertension

The cause of chronic thromboembolic pulmonary hypertension is unknown and there is no specific circulating biomarker for its detection. The aim of the present study was to use proteomic analysis to detect serum biomarkers by evaluating the serum profiles of low-molecular-weight peptides using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry in patients with chronic thromboembolic pulmonary hypertension. Serum low-molecular-weight peptide profiling using the spectrophotometric technique was studied retrospectively in patients with chronic thromboembolic pulmonary hypertension and in controls matched for sex and age. The serum level of a 2989-Da peptide in the sera of patients was significantly higher compared to that of controls. Tandem mass spectrometry indicated that the peptide was a fragment of fibrinogen Aα chain (KMADEAGSEADHEGTHSTKRGHAKSRPV). The serum level of fibrinogen Aα chain fragment, measured using a heavy isotope internal standard, tended toward negative correlation with plasmin-α2-plasmin inhibitor complex (P=0.073) and had a positive correlation with thrombin-anti-thrombin complex (P=0.031). This fragment may be a potential diagnostic biomarker for chronic thromboembolic pulmonary hyper-tension.

New serum biomarkers for detection of esophageal carcinoma using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

To screen for the potential protein biomarkers in serum for the diagnosis of esophageal carcinoma (EC) using proteomic fingerprint technology. Proteomic fingerprint technology combining magnetic beads with MALDI-TOF-MS was used to profile and compare the serum proteins from 78 patients with EC and 95 healthy blood donors. Proteomic patterns associated with EC were identified by Biomarker Patterns Software. Model of biomarkers was constructed and evaluated using the Biomarker Patterns Software. A total of 60 discriminating m/z peaks were identified that were related to EC (P < 0.01). The model of biomarkers constructed by the Biomarker Patterns Software based on the four biomarkers (2049.6, 3936.5, 5339.9, and 13748.8 Da) generated excellent separation between the EC and control groups. The sensitivity was 92.5% and the specificity was 88%. Blind test data indicated a sensitivity of 89.5% and a specificity of 84.4%. Biomarkers for EC can be discovered in serum by MALDI-TOF-MS combining the use of magnetic beads. The pattern of combined markers provides a powerful and reliable diagnostic method for EC with a high sensitivity and specificity.