Cardiovascular biomarkers in body fluids: progress and prospects in optical sensors

Cardiovascular diseases (CVD) are the major causative factors for high mortality and morbidity in developing and developed nations. The biomarker detection plays a crucial role in the early diagnosis of several non-infectious and life-threatening diseases like CVD and many cancers, which in turn will help in more successful therapy, reducing the mortality rate. Biomarkers have diagnostic, prognostic and therapeutic significances. The search for novel biomarkers using proteomics, bio-sensing, micro-fluidics, and spectroscopic techniques with good sensitivity and specificity for CVD is progressing rapidly at present, in addition to the use of gold standard biomarkers like troponin. This review is dealing with the current progress and prospects in biomarker research for the diagnosis of cardiovascular diseases.Expert opinion.Fast diagnosis of cardiovascular diseases (CVDs) can help to provide rapid medical intervention, which can affect the patient’s short and long-term health. Identification and detection of proper biomarkers for early diagnosis are crucial for successful therapy and prognosis of CVDs. The present review discusses the analysis of clinical samples such as whole blood, blood serum, and other body fluids using techniques like high-performance liquid chromatography-LASER/LED-induced fluorescence, Raman spectroscopy, mainly, optical methods, combined with nanotechnology and micro-fluidic technologies, to probe patterns of multiple markers (marker signatures) as compared to conventional techniques.     

Current and proposed biomarkers of anthracycline cardiotoxicity in cancer: emerging opportunities in oxidative damage and autophagy

A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention". Biomarkers can be utilized to detect disease, evaluate treatment risks, or determine treatment effectiveness. In the case of cancer, anthracyclines such as doxorubicin are front-line therapy to treat a number of different malignancies including breast cancer. However, a significant fraction of patients experience drug-induced cardiotoxicity. This toxicity is dose-limiting and can cause long-term morbidity or mortality. There is an unmet medical need to identify patients who are at risk for doxorubicin-induced cardiotoxicity, to detect cardiac damage early so that patient risk can be minimized, and to monitor the success of cardioprotective strategies. Therefore, doxorubicin treatment of cancer is an excellent example of the need for biomarkers to indicate drug safety in addition to drug efficacy. In this review we will discuss the mechanism of doxorubicinassociated cardiotoxicity, as well as other cancer therapies that induce cardiac toxicity by causing oxidative damage. We will also evaluate established and proposed biomarkers for cardiotoxicity based on our evolving knowledge of oxidative damage and subsequent autophagy. Finally, we will discuss advantages of combining oxidative damage- and autophagy-based protein biomarkers with current biomarkers such as troponins to facilitate early detection and mitigation of cardiotoxicity induced by cancer therapeutic agents.     

Proteomic profiling of pancreatic cancer for biomarker discovery

Pancreatic cancer is a uniformly lethal disease that is difficult to diagnose at early stage and even more difficult to cure. In recent years, there has been a substantial interest in applying proteomics technologies to identify protein biomarkers for early detection of cancer. Quantitative proteomic profiling of body fluids, tissues, or other biological samples to identify differentially expressed proteins represents a very promising approach for improving the outcome of this disease. Proteins associated with pancreatic cancer identified through proteomic profiling technologies could be useful as biomarkers for the early diagnosis, therapeutic targets, and disease response markers. In this article, we discuss recent progress and challenges for applying quantitative proteomics technologies for biomarker discovery in pancreatic cancer.     

Discovery and Validation of Clinical Biomarkers of Cancer: A Review Combining Metabolomics and Proteomics

Early detection and diagnosis of cancer can allow timely medical intervention, which greatly improves chances of survival and enhances quality of life. Biomarkers play an important role in assisting clinicians and health care providers in cancer diagnosis and treatment follow‐up. In spite of years of research and the discovery of thousands of candidate cancer biomarkers, only a few have transitioned to routine usage in the clinic. This review highlights advances in proteomics technologies that have enabled high rates of discovery of candidate cancer biomarkers and evaluates integration with other omics technologies to improve their progress through to validation and clinical translation. Furthermore, it gauges the role of metabolomics technology in cancer biomarker research and assesses it as a complementary tool in aiding cancer biomarker discovery and validation.     

The use of biomarkers in surveillance, medical screening, and intervention

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.     

Urinary proteomics and molecular determinants of chronic kidney disease: possible link to proteases

Chronic kidney disease (CKD) is the gradual decrease in renal function. Currently available biomarkers are effective only in detecting late stage CKD. Biomarkers of early stage CKD and prognostic biomarkers are required. We review the major findings in urinary proteomics in CKD during the last five years. Significant progress has been made and today urinary proteomics is applied in large randomized trials, and in patient management. Many of the biomarkers indicate altered protease activity. We therefore also review the literature on proteases associated with renal function loss. We anticipate in silico prediction tools of protease activity and additional system biology studies may contribute to biomarker discovery and elucidate the role of proteases in CKD development and progression. These approaches will enable the deciphering of the molecular pathophysiology of CKD, and hence definition of the most appropriate therapeutic targets in the future. Together with stable biomarker panels available today, this will significantly improve patient management.     

Biomarkers for early detection of breast cancer: what, when, and where?

Early detection of breast cancer reduces the suffering and cost to society associated with the disease. A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. The earlier and more accurate the diagnostic biomarker can predict disease onset, the more valuable it becomes. Here, a brief review of existing and emerging approaches for breast cancer biomarker identification and analysis is presented. Those biomarkers found in biological fluids, blood in particular, apparently hold the best promise for fast development of screening assays. Autoantibodies and abnormal tumor-specific DNA methylation found in cell-free plasma DNA may provide the best opportunity for constructing multiplexed and highly redundant tests, which will be sufficiently specific and sensitive for early detection of breast cancer. It is expected that technologies developed for breast cancer detection will be useful for other types of cancer.     

尿液作为新型生物标志物来源的探索

机体各种变化是生物标志物研究的核心内容.因为机体固有的稳态调控机制,在血液中早期产生的变化容易被清除.而在尿液中不存在稳态调控机制,允许容纳更多的变化因素存在.尤其在疾病发生的早期阶段,从尿液中更有可能发现新型的早期生物标志物.在尿液生物标志物研究中,亦应当考虑药物的影响.使用尿液生物标志物研究路线图,能够有效规避各种影响因素对于尿液生物标志物研究的干扰;同时,结合膜处理新技术,有利于经济、高效地大规模收集尿液样本,促进尿液生物标志物的大规模研究.另外,本文介绍了最容易在尿液中体现出变化的肾脏疾病生物标志物的研究进展.尿液生物标志物的研究,将赋予人类在疾病预防、诊断、治疗及预后监测等诸多方面实现更多进步的可能性.     

Preclinical strategies to define predictive biomarkers for therapeutically relevant cancer subtypes

Defining key driver mutations in cancer, the resulting aberrations in molecular mechanisms and the subsequent phenotype underpins the development and implementation of novel personalized medicine strategies. The literature is replete with biomarkers of prognosis and therapeutic responsiveness identified in single cohorts of patients that have not been independently validated and as a consequence, not developed. Integrating companion biomarker discovery with therapeutic development at the preclinical stage creates the opportunity to identify candidate biomarkers early, which would significantly facilitate both biomarker and therapeutic development. Advances in “-omic” technologies have led to large-scale efforts in characterizing and cataloguing the full range of aberrations in cancer. These include the International Cancer Genome Consortium and The Cancer Genome Atlas, which aim to comprehensively catalogue the range of genomic aberrations for large numbers of cancers for a progressively increasing range of cancer types and subtypes. The technical challenges associated with achieving these goals in some instances have required the generation of primary xenografts and cell lines. These extensively characterized model systems will provide an unprecedented resource for the discovery of biomarkers of therapeutic responsiveness for established therapies, and the development of companion biomarkers linked with preclinical novel therapeutic development in the future.     

Proteomics approaches to urologic diseases

Biomarkers are greatly needed for several urologic diseases, such as interstitial cystitis, the symptomatic and clinical progression of benign prostate hyperplasia, as well as the specific detection of urologic cancers, including prostate and bladder cancer. This review aims to: briefly describe the need for biomarkers in the field and biomarkers that are currently available for clinicians; address the limitations and roadblocks to effective biomarker discovery; and provide examples and strategies for implementing biomarkers in clinical practice and/or drug discovery.     

Proteomics in prostate cancer biomarker discovery

Despite advances in molecular medicine, genomics, proteomics and translational research, prostate cancer remains the second most common cause of cancer-related mortality for men in the Western world. Clearly, early detection, targeted treatment and post-treatment monitoring are vital tools to combat this disease. Tumor markers can be useful for diagnosis and early detection of cancer, assessment of prognosis, prediction of therapeutic effect and treatment monitoring. Such tumor markers include prostate-specific antigen (prostate), cancer antigen (CA)15.3 (breast), CA125 (ovarian), CA19.9 (gastrointestinal) and serum α-fetoprotein (testicular cancer). However, all of these biomarkers lack sensitivity and specificity and, therefore, there is a large drive towards proteomic biomarker discovery. Current research efforts are directed towards discovering biosignatures from biological samples using novel proteomic technologies that provide high-throughput, in-depth analysis and quantification of the proteome. Several of these studies have revealed promising biomarkers for use in diagnosis, assessment of prognosis, and targeting treatment of prostate cancer. This review focuses on prostate cancer proteomic biomarker discovery and its future potential.     

Biomarkers of neurodegenerative disorders： How good are they？

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies,biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differentiable between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance,are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer‘s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson‘s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington‘s gene mutations in Huntington‘s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.     

Proteomics for early detection of colorectal cancer: recent updates

Introduction: Colorectal cancer (CRC) is a common type of cancer with a relatively poor survival rate. The survival rate of patients could be improved if CRC is detected early. Biomarkers associated with early stages of tumor development might provide useful tools for the early diagnosis of colorectal cancer.

Areas covered: Online searches using PubMed and Google Scholar were performed using keywords and with a focus on recent proteomic studies. The aim of this review is to highlight the need for biomarkers to improve the detection rate of early CRC and provide an overview of proteomic technologies used for biomarker discovery and validation. This review will also discuss recent proteomic studies which focus on identifying biomarkers associated with the early stages of CRC development.

Expert commentary: A large number of CRC biomarkers are increasingly being identified by proteomics using diverse approaches. However, the clinical relevance and introduction of these markers into clinical practice cannot be determined without a robust validation process. The size of validation cohorts remains a major limitation in many biomarker studies.     

Role of kidney biomarkers of chronic kidney disease: An update

Chronic kidney disease (CKD) is a progressive pathological condition marked by deteriorating renal function over time. Diagnostic of kidney disease depend on serum creatinine level and glomerular filtration rate which is detectable when kidney function become half. The detection of kidney damage in an early stage needs robust biomarkers. Biomarkers allow monitoring the disease progression at initial stages of disease. On the onset of impairment in cellular organization there is perturbation in signaling molecules which are either up-regulated or down-regulated and act as an indicator or biomarker of diseased stage. This review compiled the cell signaling of different kidney biomarkers associated with the onset of chronic kidney diseases. Delay in diagnosis of CKD will cause deterioration of nephron function which leads to End stage renal disease and at that point patients require dialysis or kidney transplant. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in CKD will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for CKD.     

The promise of biomarkers in cancer screening and detection

Despite the recent decline in the incidence of cancer, long-term mortality rates remain unchanged. One of the most important factors in the survival of cancer is detection at an early stage. Clinical assays that detect the early events of cancer offer an opportunity to intervene and prevent cancer progression. Biomarkers are important molecular signatures of the phenotype of a cell that aid in early cancer detection and risk assessment. Although new information and technologies are clearly important for new biomarker discovery, we face major hurdles in translating new findings into clinical application. Here, we discuss examples of recent advances and limitations in cancer biomarker identification and validation, and the implications for cancer prevention.     

Current progress in protein profiling of complex samples

Accurate cancer biomarkers are needed for early detection, disease classification, prediction of therapeutic response and monitoring treatment. While there appears to be no shortage of candidate biomarker proteins, a major bottleneck in the biomarker pipeline continues to be their verification by enzyme linked immunosorbent assays. Multiple reaction monitoring (MRM), also known as selected reaction monitoring, is a targeted mass spectrometry approach to protein quantitation and is emerging to bridge the gap between biomarker discovery and clinical validation. Highly multiplexed MRM assays are readily configured and enable simultaneous verification of large numbers of candidates facilitating the development of biomarker panels which can increase specificity. This review focuses on recent applications of MRM to the analysis of plasma and serum from cancer patients for biomarker verification. The current status of this approach is discussed along with future directions for targeted mass spectrometry in clinical biomarker validation.     

Inconvenient truth: Cancer biomarker development by using proteomics

A biomarker is a crucial tool for measuring the progress of disease and the effects of treatment for better clinical outcomes in cancer patients. Diagnostic, predictive, and prognostic biomarkers are required in various clinical settings. The proteome, a functional translation of the genome, is considered a rich source of biomarkers; therefore, sizable time and funding have been spent in proteomics to develop biomarkers. Although significant progress has been made in technologies toward comprehensive protein expression profiling, and many biomarker candidates published, none of the reported biomarkers have proven to be beneficial for cancer patients. The present deceleration in biomarker research can be attributed to technical limitations. Additional efforts are required to further technical progress; however, there are many examples demonstrating that problems in biomarker research are not so much with the technology but in the study design. In the study of biomarkers for early diagnosis, candidates are screened and validated by comparing cases and controls of similar sample size, and the low prevalence of disease is often ignored. Although it is reasonable to take advantage of multiple rather than single biomarkers when studying diverse disease mechanisms, the annotation of individual components of reported multiple biomarkers does not often explain the variety of molecular events underlying the clinical observations. In tissue biomarker studies, the heterogeneity of disease tissues and pathological observations are often not considered, and tissues are homogenized as a whole for protein extraction. In addition to the challenge of technical limitations, the fundamental aspects of biomarker development in a disease study need to be addressed. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.     

Predictive and therapeutic biomarkers in chimeric antigen receptor T-cell therapy: A clinical perspective

The adoptive transfer of genetically engineered T cells modified to express a chimeric antigen receptor (CAR) has shown remarkable activity and induces long-term remissions in patients with advanced hematologic malignancies. To date, little is known about predictive indicators of therapeutic efficacy or serious toxicity after CAR T-cell therapy in clinical practice. Biomarkers are not only potentially able to inform physicians and researchers of immunotherapy targets in particular but could also be used to monitor the effectiveness of treatments and to predict incidence of side effects in some circumstances. Identification of new biomarkers can therefore not only contribute to the development of new therapeutic and prognostic strategies for CAR T-cell therapy for cancer but also help to generate improved clinical practices for early recognition and minimization of adverse effects while preserving the antitumor activity of the CAR T cells. Herein, we will consider a variety of predictive and therapeutic biomarkers in CAR T-cell therapy and the state of current understanding of their clinical utility. The incorporation of biomarker studies in CAR T-cell clinical trials and practice will help to realize the potential clinical benefit of biomarker-guided therapy.