Tissular and soluble miRNAs for diagnostic and therapy improvement in digestive tract cancers.

摘要

Digestive cancers (e.g., gastric, colorectal, pancreatic or hepatocarcinoma) are among the most frequently reported cancers in the world, and are characterized by invasivity, metastatic potential and poor outcomes. This group includes some of the most critical cancers (among them, are those ranked second to forth in cancer-related mortality) and, despite all sustained efforts, they maintain a profile of low survival rates and lack successful therapies. Discovery of biomarkers that improve disease characterization may make optimized or personalized therapy possible. Novel biomarkers are expected to provide, hopefully, less-invasive or noninvasive diagnostic tools that make possible earlier detection of disease. Also, they may provide a more reliable selection instrument in the drug discovery process. miRNAs, short noncoding RNAs, have emerged in the last few years as significant regulators of cellular activities, controlling protein expression at the post-transcriptional level, with a significant implication in pathology in general and, of most relevance, in cancers. Deregulation of miRNA expression levels and some genetic alterations were demonstrated in various cancers, including digestive cancers. Investigations in tissue samples have provided a considerable amount of knowledge, identifying altered expressions of miRNAs associated with tumorigenesis and tumor progression. Overexpression of some tumor-inducing or tumor-promoting miRNAs was demonstrated, as well as the downregulation of tumor-suppressor miRNAs. Both individual miRNAs, as well as sets of multiple miRNAs, were set up as candidate biomarkers for diagnostics or monitoring, offering relevant insights into tumorigenic mechanisms. Circulating miRNAs were demonstrated as valuable instruments in tumor diagnosis and the prognosis of digestive cancers (affecting the esophagus, stomach, intestine, colorectum, liver and pancreas), and are being investigated thoroughly in order to generate and validate less-invasive diagnostic tools with enhanced sensitivity.