The role of Micro-RNAs in Hepatocellular Carcinoma: From Molecular Biology to Treatment

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in many biological processes, from development and cell-cycle regulation to apoptosis. miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the cellular function of their targets. Moreover, they are frequently dysregulated in HCC. In this review we summarize the latest findings of miRNAs regulation in HCC and their role as potentially diagnostic and prognostic biomarkers for HCC. We highlight development of miRNAs as potential therapeutic targets for HCC

Identifying MicroRNAs Panel Associated With Hepatocellular Carcinoma in Serum of Chronic Hepatitis C Patients

Introduction: early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this poorly diagnosed widely-spread disease. Dysregulation in microRNA (miRNAs) expression is associated with HCC progression. Objective: Is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Methodology: Candidate miRNAs were selected using bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE- miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424 and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV and 72 HCV-associated HCC patients using real time PCR (qPCR). Results: There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. While miR-199a and miR-183 showed differential expression in cirrhotic relative to non-cirrhotic patients. A panel of 5 miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). Conclusion: MiR-142, miR-183, miR-199a, miR-224 and miR-424 novel panel could serve as non-invasive biomarker for HCC early prediction in chronic HCV patients

Biomarker-Based Targeted Therapeutics

Cancer biomarkers are emerging as important tools for disease diagnosis, prediction and prognosis. A significant number of studies have been reported in the field of biomarker discovery due to their potential as personalized targeted therapy. With the converging gap about their utilization as specific targets, studies have focused on identifying disease-specific biomarkers in different cancer types. This chapter provides a comprehensive overview about different cancer-associated biomarkers, their prevalence in different cancer types and their use as targeted therapy. Additionally, we provide an in-sight on the therapeutic and diagnostic potential of different noncoding RNAs as cancer biomarkers

MicroRNA as Biomarkers in Cancer Diagnostics and Therapy

This Special Issue celebrates the 25th anniversary of the discovery of the first microRNA. The size of the microRNome and complexity of animal body plans and organ systems suggests a role for microRNAs in cell fate determination and differentiation. More than 2000 sequences have been proposed to represent unique microRNA genes in humans, with an increasing number of mechanistic roles identified in developmental, physiological, and pathological processes. Thus, dysregulation of a few key microRNAs can have a profound global effect on the gene expression and molecular programs of a cell. This great potential for clinical intervention has captured the interest and imagination of researchers in many fields. However, very few fields have been as prolific as the field of cancer research. This Special Issue provides but a glimpse of the large body of literature of microRNA biology in cancer research, containing 4 original research studies and 4 review articles that focus on specific hematologic or solid tumors in disease. Collectively, these articles highlight state-of-the-art approaches and methodologies for microRNA detection in tissue, blood, and other body fluids in a range of biomarkers applications, from early cancer detection to prognosis and treatment response. The articles also address some of the challenges regarding clinical implementation

Hepatocellular carcinoma

Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches

EPMA position paper in cancer:current overview and future perspectives

At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision

Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents one of the most significant global health issues, given its high prevalence and the challenging nature and physiology of the liver and hepatic surgery, in its many forms. This means that the most appropriate management for HCC should incorporate a multidisciplinary approach, combining the expertise from several different specialties. This book showcases the various steps in the development, diagnosis, staging, and management of HCC and provides views and thoughts from true experts in the field. As such, it is a useful resource for any physician or surgeon, whether training or practicing, who is interested in caring for patients with HCC

Role of miRNAs in Cancer

MicroRNAs are the best representatives of the non-coding part of the genome and their functions are mostly linked to their target genes. During the process of carcinogenesis, both dysregulation of microRNAs and their target genes can explain the development of the disease. However, most of the target genes of microRNAs have not yet been elucidated. In this book, we add new information related to the functions of microRNAs in various tumors and their associated targetome

Cancer Biomarkers and Targets in Digestive Organs

Identification and development of cancer biomarkers and targets have greatly accelerated progress towards precision medicine in oncology. Studies of tumor biology have not only provided insights into the mechanisms underlying carcinogenesis, but also led to discovery of molecules that have been developed into cancer biomarkers and targets. Multi-platforms for molecular characterization of tumors using next-generation genomic sequencing, immunohistochemistry, in situ hybridization, and blood-based biopsies have greatly expanded the portfolio of potential biomarkers and targets. These cancer biomarkers have been developed for diagnosis, early detection, prognosis, and prediction of treatment response. The molecular targets have been exploited for anti-cancer therapy and delivery of therapeutic agents. This Special Issue of Biomedicines focuses on recent advances in the discovery, characterization, translation, and clinical application of cancer biomarkers and targets in malignant diseases of the digestive system. The goal is to stimulate basic and translational research and clinical collaboration in this exciting field with the hope of developing strategies for prevention and early detection/diagnosis of cancer in digestive organs, and improving therapeutic and psychosocial outcomes in patients with these malignant diseases