Salivary protein biomarkers for head and neck cancer

ABSTRACT

Introduction: Saliva has gained attention as an important diagnostic fluid because it contains biomolecules that have the potential to detect early-stage cancer or to monitor the response to treatment in patients. Several saliva-based proteins have been proposed as potential biomarkers for head and neck cancers (HNC).

Areas covered: This review aims to provide an update on saliva-based protein biomarkers for HNC, often studied in observational research and clinical trials.

Expert opinion: Despite the increasing number of studies relating to salivary proteins as biomarkers for HNC, there is no consensus regarding which proteins have the best clinical utility. Most studies have analyzed individual proteins and not a protein panel approach. It must be considered that combining different proteins as a panel can increase the accuracy and will have the potential to change the current clinical practice for HNC patients.     

The potential of circulating exosomal RNA biomarkers in cancer

ABSTRACT

Introduction

There are great potentials of using exosomal RNAs (exoRNA) as biomarkers in cancers. The isolation of exoRNA requires the use of ultracentrifugation to isolate cell-free RNA followed by detection using real-time PCR, microarray, next-generation sequencing, or Nanostring nCounter system. The use of exoRNA enrichment panels has largely increased the detection sensitivity and specificity when compared to traditional diagnostic tests. Moreover, using exoRNA as biomarkers can assist the early detection of chemo and radioresistance cancer, and in turn opens up the possibility of personalized treatment to patients. Finally, exoRNA can be detected at an early stage of cancer recurrence to improve the survival rate.     

Update on urine as a biomarker in cancer: a necessary review of an old story

ABSTRACT

Introduction: Cancer causes thousands of deaths worldwide each year. Therefore, monitoring of health status and the early diagnosis of cancer using noninvasive assays, such as the analysis of molecular biomarkers in urine, is essential. However, effective biomarkers for early diagnosis of cancer have not been established in many types of cancer.

Areas covered: In this review, we discuss recent findings with regard to the use of urine composition as a biomarker in eleven types of cancer. We also highlight the use of urine biomarkers for improving early diagnosis.

Expert opinion: Urinary biomarkers have been applied for clinical application of early diagnosis. The main limitation is a lack of integrated approaches for identification of new biomarkers in most cancer. The utilization of urinary biomarker detection will be promoted by improved detection methods and new data from different types of cancers. With the development of precision medicine, urinary biomarkers will play an increasingly important clinical role. Future early diagnosis would benefit from changes in the utilization of urinary biomarkers.     

范可尼贫血的研究进展与国际诊断标准

范可尼贫血是常染色体隐性遗传性疾病（除B亚型外,X-性连锁）。临床表现为多样化的型体及智力发育异常,多种肿瘤高发倾向,进行性骨髓衰竭以及多种脏器受累。范可尼贫血的研究是医学研究当中发展最快的领域之一。迄今为止,15个不同的互补亚型被鉴别,这15个突变的基因已被定位于不同的染色体住点上。以发病机理、诊断技术、治疗为主的探索性研究日益深入,因此极大地推动了基础研究和临床诊断与治疗进展,同时也为癌症和老化方面的研究带来极大的有意义的启发。由于范可尼贫血患者大多是在发生骨髓衰竭或合并为肿瘤的晚期才为就诊的原因,所以被称之为不治之症。包括从产前开始的早期诊断,早期治疗延长生命非常重要。也由于该病的基因型及临床表型相当复杂,缺乏明显特征,所以给早期诊断带来困难与挑战。同时也要求医务人员具有血液、遗传及肿瘤等多方面的综合知识。该文将对范可尼贫血的新的概念、临床诊断、实验室检测策略等一些相关问题进行讨论,希望对国内开展此方面的工作有些帮助。     

MicroRNAs in HPV associated cancers: small players with big consequences

Introduction: MicroRNAs (miRs) are short (~20 nucleotides) non-coding ribonuecleic acids (ncRNAs) known to be involved in cellular processes such as proliferation, differentiation, immune response, pathogenicity and tumourigenesis, among many others. The regulatory mechanisms exerted by miRs have been implicated in many cancers, including Human Papillomavirus (HPV)-associated cancers.

Areas covered: In this review, the authors discuss the involvement of miRs (?143, ?375, ?21, ?200, ?296 etc.) that have been shown to be dysregulated in HPV-associated cancers. This review also encompasses both intracellular and exosomal miRs, and their potential as diagnostic biomarkers in saliva and blood. The authors have also attempted to dissect the functional impact of miRs on cellular processes such as changes in cellular polarity, loss of apoptosis and tumour suppression, and unchecked and uncontrolled cell cycle regulation, all of which ultimately lead to aberrant cellular proliferation.

Expert commentary: Identification of dysregulated miRs in HPV-associated cancers opens up new opportunities to develop diagnostic, therapeutic and prognostic biomarkers. Studies on global expression patterns of miRs dysregulated in HPV-associated cancers can be instrumental in developing broader therapeutic strategies. Therapies like anti-miR, miR-replacement and those based on alternative natural products targeting miRs, need to be improved and better synchronized to be cost-effective and have better treatment outcomes.     

Molecular biomarkers for cancer detection in blood and bodily fluids

Cancer is a major and increasing public health problem worldwide. Traditionally, the diagnosis and staging of cancer, as well as the evaluation of response to therapy have been primarily based on morphology, with relatively few cancer biomarkers currently in use. Conventional biomarker studies have been focused on single genes or discrete pathways, but this approach has had limited success because of the complex and heterogeneous nature of many cancers. The completion of the human genome project and the development of new technologies have greatly facilitated the identification of biomarkers for assessment of cancer risk, early detection of primary cancers, monitoring cancer treatment, and detection of recurrence. This article reviews the various approaches used for development of such markers and describes markers of potential clinical interest in major types of cancer. Finally, we discuss the reasons why so few cancer biomarkers are currently available for clinical use.     

Roles of exosomes in diagnosis and treatment of colorectal cancer

Exosomes are extracellular vesicles that mediate intercellular communication. They contain different molecules, such as DNA, RNA, lipid, and protein, playing essential roles in the pathogenesis of colorectal cancer (CRC). Exosomes derived from CRC are implicated in tumorigenesis, chemotherapy resistance, and metastasis. Besides, they can enhance CRC progression by increasing tumor cell proliferation, reducing apoptosis mechanistically through altering particular essential regulatory genes, or controlling several signaling pathways. Therefore, exosomes derived from CRC are essential biomarkers and can be used in the diagnosis. Indeed, it is crucial to understand the role of exosomes in CRC, which is necessary to develop diagnostic and therapeutic strategies for early detection and treatment. In the present review, we discuss the roles of exosomes in the diagnosis and treatment of CRC.     

Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers

Specific and sensitive non-invasive biomarkers for the detection of human epithelial malignancies are urgently required to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are 19-24 nt noncoding RNAs that are frequently dysregulated in cancer and have shown great promise as tissue-based markers for cancer classification. Once thought to be unstable RNA molecules, miRNAs are now shown to be stably expressed in serum, plasma, urine, saliva, and other body fluids. Moreover, the unique expression patterns of these circulating miRNAs are correlated with certain human diseases, including various types of cancer. Therefore, tumor-derived miRNAs in serum or plasma are emerging as novel blood-based fingerprints for the detection of human cancers, especially at an early stage. This review presented newly uncovered cellular and molecular mechanisms of the sources and stability of circulating miRNAs, revealing their great potential as a class of highly specific and sensitive biomarkers for tumor classification and prognostication. Meanwhile, this review also addressed certain critical issues that hinder the wide application of this new approach. Some potential challenges for the transition of circulating miRNAs from a research setting to a clinical application were also highlighted, with a future perspective of the incorporation of circulating miRNAs in the field of clinical oncology, especially their great potential from diagnostic to prognostic and predictive applications.     

Biomarkers and acute brain injuries: interest and limits

For patients presenting with acute brain injury (such as traumatic brain injury, subarachnoid haemorrhage and stroke), the diagnosis and identification of intracerebral lesions and evaluation of the severity, prognosis and treatment efficacy can be challenging. The complexity and heterogeneity of lesions after brain injury are most probably responsible for this difficulty. Patients with apparently comparable brain lesions on imaging may have different neurological outcomes or responses to therapy. In recent years, plasmatic and cerebrospinal fluid biomarkers have emerged as possible tools to distinguish between the different pathophysiological processes. This review aims to summarise the plasmatic and cerebrospinal fluid biomarkers evaluated in subarachnoid haemorrhage, traumatic brain injury and stroke, and to clarify their related interests and limits for diagnosis and prognosis. For subarachnoid haemorrhage, particular interest has been focused on the biomarkers used to predict vasospasm and cerebral ischaemia. The efficacy of biomarkers in predicting the severity and outcome of traumatic brain injury has been stressed. The very early diagnostic performance of biomarkers and their ability to discriminate ischaemic from haemorrhagic stroke were studied.     

Saliva as a diagnostic tool for dental caries,periodontal disease and cancer: is there a need for more biomarkers?

ABSTRACT

Introduction: A biomarker is a biological indicator of normal or pathogenic processes. Identification of biomarkers is useful for the prevention, diagnosis and prognosis of diseases as well as for monitoring the progression of pathological disorders. Several types of molecules present in biological fluids can act as biomarkers such as DNA, coding and non-coding RNA, lipids, metabolites, proteins and even microbes. In this context, saliva emerges as a useful diagnostic tool for the detection of biomarkers involved with oral and systemic diseases, since it reflects the pathophysiological conditions of the organism and allows early, rapid, practical and noninvasive detection of biomarkers.

Areas covered: This review discusses the properties of saliva as a diagnostic tool and addresses the main identified biomarkers related to dental caries, periodontal disease, head and neck cancer and other types of cancer of considerable incidence among the world population.

Expert commentary: Despite extensive efforts which have been directed toward the identification of one or a combination of biomarkers with good predictive values for the early detection of dental caries, periodontal disease and cancer, these biomarkers still need validation before chairside point-of-care devices can be widely used in the clinic.     

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called ‘exosomes’, which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches.     

Predictions for the future of kallikrein-related peptidases in molecular diagnostics

Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer’s disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research.     

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.     

Genetic biomarkers for migraine

Biomarkers are physical signs or laboratory measurements that occur in association with a pathological process and have putative diagnostic and/or prognostic utility. In migraine, clinical, radiological, and biochemical biomarkers might be helpful to improve diagnosis, get insight in pathophysiology, and facilitate treatment choices. Genetic biomarkers are defined as genetic variations (mutations or polymorphisms) that can predict disease susceptibility, disease outcome, or treatment response. As yet, only a few genetic biomarkers for migraine are available. Mutations in 3 different genes responsible for familial hemiplegic migraine, a monogenetic subtype of migraine with aura, and the MTHFR C677T polymorphism in common forms of migraine are clear examples. Many positive findings from linkage studies and association studies in common forms of migraine have not been replicated, and are therefore of less clinical use. In this review, we will discuss genetic biomarkers in migraine.     

Epigenetic and genetic alterations-based molecular classification of head and neck cancer

The long-term survival rates for patients diagnosed with advanced head and neck cancer (HNC) remain poor. Many perplexing factors, including etiology and comorbidity, lead to different molecular malfunctions of HNC cells and determine the prognosis of the disease. Traditional diagnostic methods are limited in that they fail to provide an effective classification diagnosis, such as a more precise prediction of prognosis and decisions for personalized treatment regimens. Recently, molecular biology techniques, especially epigenetic and genetic techniques, have been developed that have enabled us to gain a greater insight into the molecular pathways underlying the cancers. Translating the research into a format that will facilitate effective molecular classification, support personalized treatment and determine prognosis remains a challenge. In this review, the authors provide an overview of cancer epigenetic and genetic alterations, tissue banks, and several promising biomarkers or candidates that may ultimately prove to be beneficial in a clinical setting for patients with HNC.     

Regulation of oncogenic genes by MicroRNAs and pseudogenes in human lung cancer

Lung cancer is one of the most common mortal cancer types both for men and women. Several different biomarkers have been analyzed to reveal lung cancer prognosis pathways for developing efficient therapeutics and diagnostic agents. microRNAs (miRNAs) and pseudogenes are critical biomarkers in lung cancer and alteration of their expression levels has been identified in each step of lung cancer tumorigenesis. miRNAs and pseudogenes are crucial gene regulators in normal cells as well as in lung cancer cells, and they have both oncogenic and tumor-suppressive roles in lung cancer tumorigenesis. In this study, we have determined the relationship between lung cancer related oncogenes and miRNAs along with pseudogenes in lung cancer, and the results indicate their potential as biological markers for diagnostic and therapeutic purposes.     

Simultaneous multiple early cancers of esophagus and stomach treated by endoscopic mucosal resection

Endoscopic mucosal resection (EMR) has been accepted as a completely curative treatment of gastrointestinal mucosal cancers. With advances in diagnostic techniques, the tendency to detect simultaneous multiple primary cancers is increasing. Patients with another cancer coexisting with esophageal cancer have had a poor prognosis, but if both cancers are detected in the early stage, complete treatment consisting only of endoscopic surgery, with a good prognosis, is expected. We describe two cases of simultaneous multiple early cancers of the stomach and esophagus, treated by EMR.