microRNA. Diagnostic Perspective

Biomarkers are biological measures of a biological state. An ideal marker should be safe and easy to measure, cost efficient, modifiable with treatment, and consistent across gender and ethnic groups. To date, none of the available biomarkers satisfy all of these criteria. In addition, the major limitations of these markers are low specificity, sensitivity, and false positive results. Recently identified, microRNAs (miRNAs) are endogenous, evolutionarily conserved small non-coding RNA (about 22-25 nt long), also known as micro-coordinators of gene expression, which have been shown to be an effective tools to study the biology of diseases and to have great potential as novel diagnostic and prognostic biomarkers with high specificity and sensitivity. In fact, it has been demonstrated that miRNAs play a pivotal role in the regulation of a wide range of developmental and physiological processes and their deficiencies have been related to a number of disease. In addition, miRNAs are stable and can be easily isolated and measured from tissues and body fluids. In this review, we provide a perspective on emerging concepts and potential usefulness of miRNAs as diagnostic markers, emphasizing the involvement of specific miRNAs in particular tumor types, subtypes, cardiovascular diseases, diabetes, infectious diseases, and forensic test

Current Concepts of Non-Coding RNAs in the Pathogenesis of Non-Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a relatively rare malignancy of the urinary tract system. RCC is a heterogenous disease in terms of underlying histology and its associated underlying pathobiology, prognosis and treatment schedule. The most prevalent histological RCC subtype is clear-cell renal cell carcinoma (ccRCC), accounting for about 70-80% of all RCCs. Though the pathobiology and treatment schedule for ccRCC are well-established, non-ccRCC subtypes account for 20%-30% of RCC altogether, and their underlying molecular biology and treatment options are poorly defined. The class of non-coding RNAs-molecules that are generally not translated into proteins-are new cancer drivers and suppressors in all types of cancer. Of these, small non-coding microRNAs (miRNAs) contribute to carcinogenesis by regulating posttranscriptional gene silencing. Additionally, a growing body of evidence supports the role of long non-coding RNAs (lncRNAs) in cancer development and progression. Most studies on non-coding RNAs in RCC focus on clear-cell histology, and there is a relatively limited number of studies on non-ccRCC subtypes. The aim of this review is to give an overview of the current knowledge regarding the role of non-coding RNAs (including short and long non-coding RNAs) in non-ccRCC and to highlight possible implications as diagnostic, prognostic and predictive biomarkers

The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments

Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.Instituto de Salud Carlos IIIComisión Europe

The role of microRNAs in thyroid carcinomas

Thyroid cancers (TCs) are the most common malignancies of endocrine organs. They originate from cells of different origin within the thyroid gland, which is located at the base of the neck. Several forms of TCs have been classified and great variability is observed in molecular, cellular and clinical features. The most common forms have favorable prognosis but a number of very aggressive TCs, which are characterized by a less differentiated cellular phenotype, have no effective treatment at the moment. While TC causes are not completely understood, many genetic factors involved in their onset have been discovered. In particular, activating mutations of BRAF, RET or RAS genes are known to be specifically associated with TC initiation, progression and outcome. The involvement of microRNAs in thyroid neoplasms has recently changed the paradigm for biomarker discovery in TC, suggesting that these small non-coding RNAs could be used to develop, refine or strengthen strategies for diagnosis and management of TCs. In this review, the importance of microRNA profiling in TC is explored suggesting that these molecules can be included in procedures that can perform better than any known clinical index in the identification of adverse outcomes

Clear Cell Renal Cell Carcinoma 2021–2022

Clear cell renal cell carcinoma is currently one of the most interesting areas of study in oncology. Despite the advances made in this field, this tumor continues to be a health problem of major concern in Western societies, seriously affecting public health services. Several characteristics of this tumor make it an exciting meeting point for translational collaboration between clinicians and basic researchers. Clear cell renal cell carcinoma is a paradigmatic example of inter- and intra-tumor heterogeneity from morphological, immunohistochemical, and molecular viewpoints. This tumor is also a good example to investigate the complexity of tumor/tumor and tumor/environment relationships from an ecological perspective. A deeper identification of the varied internal tumor self-organization through the specialization of cell clones and subclones as local invaders and metastasizers, on one hand, and the interactions of specific subsets of tumor cells with the local host microenvironment, on the other, will significantly enrich our knowledge of this neoplasm. Clear cell renal cell carcinoma is also a paradigmatic test bench for antiangiogenic and immune checkpoint blockage therapies. The refinement of these therapeutic tools administered alone or in combination is a hot issue in oncology, and several international trials are underway