Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma

Abstract

An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs’ validation process and routine implementation is included.

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis

“…The symptoms and signs of early CC are usually not obvious, making the diagnosis challenging, especially early identification of CIN in healthy population. Recently, miRNAs have been proved to be diagnostic biomarkers in many tumors [59,60], which might provide deep insight into BioMed Research International the diagnostic value of miRNAs for CIN and CC patients [61]. However, due to the inconsistent conclusions among those studies, as well as insufficient studies about the diagnostic value of miRNAs for CIN, we conducted this metaanalysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients.…”

microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

“…More and more studies are, indeed, associating the deregulated expression of single miRNAs or patterns of miRNAs to the aberrant expression of oncogene and tumor-suppressor genes. Although the specificity of the binding miRNA-target mRNA, each miRNA is able to target several mRNAs and, consequently, the effect of each miRNA is comprehensively wide [3].…”

“…In recent years, miRNAs are gaining increasing interest as potential biomarkers as they possess all the required characteristics of a biomarker, such as noninvasiveness, high sensitivity, specificity and predictivity, and translatability [117]. Some miRNAs have been detected in the circulation associated with metastatic breast cancer, suggesting their potential role as biomarker for discrimination between metastatic and non-metastatic breast cancers, as recently reviewed in [3]. For instance, elevated circulating levels of miR-10b, miR-155 and miR-34a were found in patients with metastatic breast cancer compared to patients with primary breast cancer without metastasis [118].…”

“…In this way, the miRNA-mediated responses are involved in the overall process of transformation. Noteworthy, circulating miRNAs are promising markers for cancer diagnosis, prognosis, monitoring the treatment response, and as powerful tools for personalized approaches [3]. Since their biological relevance and the more and more deepened knowledge about the biological mechanisms associated with their expression in both physiological and pathological conditions, novel therapeutic approaches targeting or inducing miRNAs are, currently, under study.…”

“…An abnormal miRNA expression is demonstrated in several disorders including tumors, and inflammatory and autoimmune diseases [3,[12][13][14]. In general terms, miRNA expression is downregulated in tumors (since they are inhibitors of gene expression) compared to their non-tumor counterparts and a few miRNAs can mark a specific neoplasia [15].…”