Biomarkers For Clinical Diagnosis Research Articles

Ambient Ionization Mass Spectrometry Measurement of Aminotransferase Activity.

A change in enzyme activity has been used as a clinical biomarker for diagnosis and is useful in evaluating patient prognosis. Current laboratory measurements of enzyme activity involve multi-step derivatization of the reaction products followed by quantitative analysis of these derivatives. This study simplified the reaction systems by using only the target enzymatic reaction and directly detecting its product. A protocol using paper spray mass spectrometry for identifying and quantifying the reaction product has been developed. Evaluation of the activity of aspartate aminotransferase (AST) was chosen as a proof-of-principle. The volume of sample needed is greatly reduced compared with the traditional method. Paper spray has a desalting effect that avoids sprayer clogging problems seen when examining serum samples by nanoESI. This very simple method does not require sample pretreatment and additional derivatization reactions, yet it gives high quality kinetic data, excellent limits of detection (60 ppb from serum), and coefficients of variation <10% in quantitation. Graphical Abstract ᅟ.

Cardiokines as Modulators of Stress-Induced Cardiac Disorders.

Almost 30 years ago, the protein, atrial natriuretic peptide, was identified as a heart-secreted hormone that provides a peripheral signal from the myocardium that communicates to the rest of the organism to modify blood pressure and volume under conditions of heart failure. Since then, additional peripheral factors secreted by the heart, termed cardiokines, have been identified and shown to coordinate this interorgan cross talk. In addition to this interorgan communication, cardiokines also act in an autocrine/paracrine manner to play a role in intercellular communication within the myocardium. This review focuses on the roles of newly emerging cardiokines that are mainly increased in stress-induced cardiac diseases. The potential of these cardiokines as clinical biomarkers for diagnosis and prognosis of cardiac disorders is also discussed.

Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer.

The most important biological function of exosomes is their possible use as biomarkers in clinical diagnosis. Compared with biomarkers identified in conventional specimens such as serum or urine, exosomal biomarkers provide the highest amount of sensitivity and specificity, which can be attributed to their excellent stability. Exosomes, which harbor different types of proteins, nucleic acids and lipids, are present in almost all bodily fluids. The molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), are promising as biomarkers in clinical diagnosis. This discovery that exosomes also contain messenger RNAs and miRNAs shows that they could be carriers of genetic information. Although the majority of RNAs found in exosomes are degraded RNA fragments with a length of <200 nucleotides, some full-length RNAs might be present that may affect protein production in the recipient cell. In addition, exosomal miRNAs have been found to be associated with certain diseases. Several studies have pointed out miRNA contents of circulating exosomes that are similar to those of originating cancer cells. In this review, the recent advances in circulating exosomal miRNAs as biomarkers in gastrointestinal cancers are discussed. These studies indicated that miRNAs can be detected in exosomes isolated from body fluids such as saliva, which suggests potential advantages of using exosomal miRNAs as noninvasive novel biomarkers.

PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer.

The incidence of prostate cancer (PCa) is rising steadily among males in many countries. Serum prostate-specific antigen (PSA) is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PCA3 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

Ghrelin and Neurodegenerative Disorders-a Review.

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

Chemiluminescence of creatinine/H2O2/Co(2+) and its application for selective creatinine detection.

Creatinine is an important biomarker in clinical diagnosis and biomonitoring programs as well as urinary metabolomic/metabonomics research. Current methods are either nonselective, time consuming or require heavy and expensive instruments. In this study, chemiluminescence of creatinine with hydrogen peroxide has been reported for the first time, and its chemiluminescence is remarkably enhanced in the presence of cobalt ions. By utilizing these phenomena, we have developed a sensitive and selective chemiluminescence method for creatinine determination by coupling with flow injection analysis. The calibration curve is linear in the range of 1×10(-7)-3×10(-5)mol/L with a limit of detection (S/N=3) of 7.2×10(-8)mol/L, which is adequate for detecting creatinine in the clinically accepted range. The relative standard deviation for seven measurements of 3×10(-5)mol/L creatinine is 1.2%. The chemiluminescence method was then utilized to detect creatinine in human urine samples after simple dilution with water. It takes less than 1min each measurement and the recoveries for spiked urine samples were 100-103%. The interference study demonstrates that some common species in urine, such as amino acids, ascorbic acid and creatine, have negligible effects on creatinine detection. The present method does not use expensive instruments, enzymes and separation technique. This method has the advantages of sensitivity, selectivity, simplicity, rapidity, and low cost. It holds great promise for basic or comprehensive metabolic panel, drug screening, anti-dopping, and urinary metabolomic/metabonomics research.

Abstract 4840: The role of miR-146a and novel Rhenium compounds on prostate cancer cell lines derived from African Americans and European American patients

Abstract African American (AA) men have disproportionately high incidence and mortality rates of prostate cancer (PCa) compared to other ethnic groups in the United States. The identification of molecular factors that contribute to this disparity could improve diagnosis and may predict therapeutic efficacy. MicroRNA-146a (miR-146a) suppresses PCa transformation from androgen-dependent to -independent state, and suppresses a kinase coding gene which reduces cell proliferation, invasion and metastasis. It is anticipated that miR-146a and other miRNAs may one day become biomarkers for clinical diagnosis and prognosis of several types of cancer including PCa. Novel rhenium compounds have shown anti-cancer properties especially in PCa. Therefore, the purpose of this study was to determine the expression of miR-146a in PCa cell lines derived from AA and European American (EA) patients. We also investigated the anti-cancer properties of two novel organorhenium pentylcarbonate (RPC) compounds. Relative levels of miRNA expression was determined by qRT-PCR, miRNA plate assay and smart flare technology after isolating total RNA from the cells and the exosomes from the tumor microenvironment. Cytotoxicity studies of the RPC compounds were done by using MTT and Trypan Blue assay. Our data showed a several fold increase in the expression of miR-146a in PCa cells derived from AA patient in comparison to cells derived from EA patients and a benign cell line. The RPC compounds showed bioactivity in all the PCa lines. To date, we are unaware of any studies that compared the miR-146a expression in PCa cells derived from the two racial groups. Our study suggests that miR-146a is up-regulated in PCa cells derived from AA patient compared to EA patient, which could possibly contribute to the aggressiveness associated in AA patients. We also found that the novel organorhenium compounds are bioactive with anti-cancer properties. Our results warrant further studies which are being done by our laboratory for assessing the mechanistic role of miR-146a associated with the anti-cancer activity of rhenium compounds and the role of miR-146a to define the racial disparity in PCa patients. Acknowledgment: This research was supported by a grant from the Borroughs Wellcome Fund, NSF-LSAMP, NIH-MARC and a Disability Supplement grant from NIH. Citation Format: Monet Stevenson, Jameel Joyner, Khadija Dildar, Oladipo Adedeji, Krishnan Prabhakaran, Hirendra N. Banerjee, Santosh Mandal, Fazlul Sarkar. The role of miR-146a and novel Rhenium compounds on prostate cancer cell lines derived from African Americans and European American patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4840. doi:10.1158/1538-7445.AM2015-4840

CE-MS-based proteomics in biomarker discovery and clinical application.

CE-MS is applied in clinical proteomics for both the identification of biomarkers of disease and assessment of biomarkers in clinical diagnosis. The analysis is reproducible, fast, and requires only small sample volumes. However, successful CE-MS analysis depends on several critical steps that can be consolidated as follows: (i) proper sample preparation and fractionation, (ii) application of suitable capillary coating and appropriate CE-MS interfaces, to ensure the reproducibility and stability of the analysis, and (iii) an optimized clinical and statistical study design to increase the chances for obtaining clinically relevant results. In this review, we cover all these aspects, and present several examples of the application of CE-MS in clinical proteomics.

Exosomes: novel biomarkers for clinical diagnosis.

Exosomes are 30–120 nm endocytic membrane-derived vesicles that participate in cell-to-cell communication and protein and RNA delivery. Exosomes harbor a variety of proteins, nucleic acids, and lipids and are present in many and perhaps all bodily fluids. A significant body of literature has demonstrated that molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), hold great promise as novel biomarkers for clinical diagnosis. In this minireview, we summarize recent advances in the research of exosomal biomarkers and their potential application in clinical diagnostics. We also provide a brief overview of the formation, function, and isolation of exosomes.

Sequential weighted Wiener estimation for extraction of key tissue parameters in color imaging: a phantom study.

Key tissue parameters, e.g., total hemoglobin concentration and tissue oxygenation, are important biomarkers in clinical diagnosis for various diseases. Although point measurement techniques based on diffuse reflectance spectroscopy can accurately recover these tissue parameters, they are not suitable for the examination of a large tissue region due to slow data acquisition. The previous imaging studies have shown that hemoglobin concentration and oxygenation can be estimated from color measurements with the assumption of known scattering properties, which is impractical in clinical applications. To overcome this limitation and speed-up image processing, we propose a method of sequential weighted Wiener estimation (WE) to quickly extract key tissue parameters, including total hemoglobin concentration (CtHb), hemoglobin oxygenation (StO2), scatterer density (α), and scattering power (β), from wide-band color measurements. This method takes advantage of the fact that each parameter is sensitive to the color measurements in a different way and attempts to maximize the contribution of those color measurements likely to generate correct results in WE. The method was evaluated on skin phantoms with varying CtHb, StO2, and scattering properties. The results demonstrate excellent agreement between the estimated tissue parameters and the corresponding reference values. Compared with traditional WE, the sequential weighted WE shows significant improvement in the estimation accuracy. This method could be used to monitor tissue parameters in an imaging setup in real time.

Abstract 3346: Development of a multiplex screening panel for Akt signaling pathway biomarkers in cell and tissue lysate models

Abstract Major challenges face the large-scale implementation of intracellular tumor biomarkers for clinical diagnosis and therapeutic development. These challenges include non-quantitative results, insufficient assay sensitivity, and lack of multiplexing capability. For many studies, sample volumes are limited (e.g., tumor lysates); however, it is essential to extract as much biomarker information as possible from a given sample while maintaining the quality and consistency necessary to sustain ongoing studies. To address these challenges, MSD® has developed multiplex panels for assaying cell signaling biomarkers using fit-for-purpose methods that emphasize optimal multiplex combinations and rigorous development of critical reagents. Here we report the development and verification of a multiplex screening panel of immunoassays for simultaneous measurement of total and phosphorylated analytes of the Akt signalling pathway using MSD technology. Markers in the panel include phosphorylated and total forms of GSK3B, p70S6K, FOXO3a, PTEN, Akt, S6RP, PRAS40, and ERK1. We demonstrate the ability of these assays to measure analyte levels in multiple tumor-derived cell lines and human tissue samples (normal and tumor) with excellent sensitivity and performance. Most analytes can be quantified using no more than 10 µg of sample. By using recombinant proteins to calibrate some of the assays, we were able to quantify analytes in cultured cell lysates, including MCF-7 and Jurkat T-cells. Lack of analyte specificity is a well-known issue when multiplexing intracellular signaling analytes, especially those in a common signaling pathway such as the Akt pathway. Through rigorous optimization, we achieved non-specific binding less than or equal to 1% for all analytes in this panel. Spike recovery and dilution linearity were characterized to demonstrate matrix tolerance in tumor cell line and tissue lysates as well as dynamic ranges between 3 and 4 logs, allowing quantification of analytes at different abundance levels without using multiple dilutions. In conclusion, MSD MULTI-SPOT® Akt signaling assay panels have been developed and verified for measurement of intracellular tumor biomarkers of relevance to clinical diagnosis, therapeutic development, and treatment of various cancers. The accuracy, reliability, ease of use, and high-throughput features of these multiplex assays make them ideally suited for use in large-scale clinical studies. Citation Format: Thomas W. Miller, Karen Tressler, Jill Dunty, Paula Eason, Leonid Dzantiev, Sripriya Ranganathan, Laura Schaefer, David Stewart, Pankaj Oberoi, Jacob Wohlstadter. Development of a multiplex screening panel for Akt signaling pathway biomarkers in cell and tissue lysate models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3346. doi:10.1158/1538-7445.AM2014-3346

Ultra-specific zeptomole microRNA detection by plasmonic nanowire interstice sensor with Bi-temperature hybridization.

MicroRNAs (miRNAs) are emerging new biomarkers for many human diseases. To fully employ miRNAs as biomarkers for clinical diagnosis, it is most desirable to accurately determine the expression patterns of miRNAs. The optimum miRNA profiling method would feature 1) highest sensitivity with a wide dynamic range for accurate expression patterns, 2) supreme specificity to discriminate single nucleotide polymorphisms (SNPs), and 3) simple sensing processes to minimize measurement variation. Here, an ultra-specific detection method of miRNAs with zeptomole sensitivity is reported by applying bi-temperature hybridizations on single-crystalline plasmonic nanowire interstice (PNI) sensors. This method shows near-perfect accuracy of SNPs and a very low detection limit of 100 am (50 zeptomole) without any amplification or labeling steps. Furthermore, multiplex sensing capability and wide dynamic ranges (100 am-100 pm) of this method allows reliable observation of the expression patterns of miRNAs extracted from human tissues. The PNI sensor offers combination of ultra-specificity and zeptomole sensitivity while requiring two steps of hybridization between short oligonucleotides, which could present the best set of features for optimum miRNA sensing method.

Development of a bead-based immunoassay to routinely measure vimentin autoantibodies in the clinical setting

IntroductionVimentin is an intermediate filament protein generally expressed in the cytosol of many adult cell types, including leukocytes, fibroblasts and endothelial cells. Several tissue and/or injury-specific isoforms of vimentin are known to exist that may trigger autoimmune responses due to aberrant structural or conformational variations. Such scenarios include allograft rejection and certain autoimmune diseases, such as rheumatoid arthritis. The primary objective for this study was to develop a Luminex immunobead assay to quantitate circulating levels of vimentin antibodies and, secondarily, to appraise the feasibility of these autoantibodies as a biomarker for clinical diagnosis. MethodsRecombinant human vimentin was conjugated to MagPlex® beads using standard carbodiimide/NHS chemistry and coupling efficiency tested and assay parameters determined using a commercial anti-vimentin polyclonal antibody. A limited number of serum samples (n=71) were then tested to evaluate the diagnostic value for future biomarker development efforts. ResultsFindings from repeated testing of three distinct batches of assays provide assay range parameters of 0.18–15μg/mL, median inter-assay recovery parameter within 1% of completion, and inter-assay variation (%CV) at 7%. The assay was found to be stable at several conditions with less than 5% loss in a month. Preliminary evaluation of the assay demonstrates significantly (p=0.022) higher circulating levels of anti-vimentin antibodies in 51 cases of renal allograft rejection relative to 20 cases of age-matched controls. ConclusionA direct capture assay for vimentin autoantibodies was developed and analytically validated. Preliminary evaluation of this assay against patient materials was promising and justifies additional testing with larger cohorts in future studies.

Correlation of Serum β2-Microglobulin Levels with Prostate-specific Antigen, Gleason Score, Clinical Stage, Tumor Metastasis and Therapy Efficacy in Prostate Cancer

Despite previous reports implying a role of β2-microglobulin (β2M) in the development of prostate cancer (PCa), the correlation of serum β2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of β2M in patients with PCa and explore the potential use of β2M as a tumor marker for diagnosis, treatment and prognosis of PCa. Serum β2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum β2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed. Our results showed that: (i) PCa patients had significantly higher levels of β2M compared to those of patients with BPH or those of healthy controls. (ii) Serum β2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of β2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum β2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease. Our results demonstrate that serum β2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum β2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa.

Assay Profiles of Prostanoids and Female Sex Hormones for Studying Potential Biomarkers of Hypertension

Aim: Prostanoids and female sex hormones play an important role in the progression of hypertension. However, their close-related structures make simultaneous separation and analyses difficult. A method was developed to separate and analyze seventeen important bioactive compounds including nine prostanoids and eight sex hormones in a short time. By applying the method to quantify prostanoids and female sex hormones in urine samples from hypertension patients, it becomes possible to find effective biomarkers for clinical diagnosis, prevention and treatment of hypertension. Materials and methods: A reversed phase high performance liquid chromatography is used to develop the separation method. A combination of up to nine prostanoids (PGD2, PGE2, 6-keto PGF1α, PGF2α, 11-dehydro TXB2, 8-iso PGF2α, 13,14-dihydro-15-keto PGA2, 13,14-dihydro-15-keto PGE2 and 15-deoxy Δ12,14 PGJ2) and eight female sex hormones (E1, E2, E3, progesterone, 2-OHE1, 4-OHE1, 16α-OHE1, and 2-MeOE1) are chosen as analytes. The separation is performed on Symmetry C18 4.6x250 mm column with 5 μm particle size. A UV detector is selected to determine the levels of analytes in a single 25-minute run. Results: The method is the first we are aware of successfully demonstrating the separation of the two different groups of bioactive compounds prostanoids and female sex hormones. It has been shown to have excellent selectivity, sensitivity, and accuracy over biologically relevant concentration ranges and has been tested on urine samples from hypertension patients.

Autoantibodies, autoimmune disease, and the birth of immune diagnostics

The appearance of autoantibody to DNA followed sequentially by the disappearance of anti-DNA and appearance of DNA antigen in a patient with systemic lupus erythematosus demonstrated that autoantibodies participate in immune complex-mediated pathogenesis. Continuing studies showed that autoantibodies are also useful biomarkers in clinical diagnosis and important reagents for elucidating the structure and function of intracellular proteins in cell biology. Recently, autoantibodies to tumor-associated antigens have been identified in cancer, and these findings have expanded the field of cancer immunodiagnostics.

Proteomics analysis in lupus erythematosus: an update

Proteomics analysis allows a comprehensive and integral understanding of occurrence of related diseases and metabolism of cells at protein level.Recently,the application of proteomics has attracted more and more attention.In detail,proteomics has been used to study the mechanisms underlying the lymphocyte abnormality in lupus erythematosus as well as keratinocyte-mediated abnormal immune reaction,to identify lupus-related autoantigens and autoantibody clusters,to look for biomarkers for clinical diagnosis such as urine hepcidin in patients with lupus nephritis,to seek drug targets,thereby to facilitate early diagnosis and treatment of lupus erythematosus. Key words: Lupus erythematosus,systemic; Proteomics; Immunity

Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy.

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.

Hippocampal Atrophy in Alzheimer’s Disease

SUMMARY New research criteria for Alzheimer’s disease (AD) and mild cognitive impairment (MCI) emphasize the use of imaging biomarkers in clinical diagnosis of these disorders. The volume loss of medial temporal lobe structures, especially hippocampal atrophy, is the best validated marker of AD. Manual tracing on MRI is the present gold standard for evaluating hippocampal volume; however, it is laborious and tracer-dependent. We categorized the most recent full- or semi-automated methods by the nature of the output of the method: size and shape of subcortical structures, cortical thickness, atrophy-rate and voxel- and region-based characteristics. The features of each method are introduced. The findings in structural MRI studies, especially in those studies utilizing the most recent methods, and the accuracies of those new methods in differentiating AD from healthy controls and stable MCI from progressive MCI are reviewed.

Serum Amyloid A Protein in Clinical Cancer Diagnosis

The serum amyloid A (SAA) protein is an acute phase protein that is synthesized under the regulation of inflammatory cytokines during both acute and chronic inflammation. It is suggested that the SAA increases correlate with many types of carcinogenesis and neoplastic diseases. Th changes in SAA in serum could therefore indicate the progress and malignancy of the disease, as well as the host responses. The present paper reviewed the rationale of using SAA as potential cancer biomarker in clinical diagnosis, including the contribution and involvement of SAA in cancer growth and development. Then we discussed the current applications of SAA in diagnosis and tracing of different types of cancers. Finally the proteomics techniques, especially the SELDI-TOF MS to identify SAA in serum from patients were appreciated as an important manner in clinical diagnosis.