Assessment of miRNA expression in cirrhosis and liver cancer

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Oncotarget published “Exosomal and non-exosomal miRNA expression levels in patients with HCV-related cirrhosis and liver cancer,” which reported that patients with HCV-related cirrhosis are at risk for developing cancer of the liver. liver. For these patients, miRNAs can serve as preclinical markers, the expression levels of which are deregulated in cancer and which are stable against damaging factors in part due to the formation of complexes with proteins or to the packaging in exosomes. The second question was whether the expression levels of miRNAs in saliva – both exosomal and non-exosomal – are associated with primary liver cancer.

These authors evaluated exosomal and non-exosomal miRNAs – let-7a-5p, -16-5p, -18a-5p, -21-5p, -22-3p, -34a-5p, -103a-3p, -122- 5p, -221-3p, -222-3p – in plasma and saliva of patients with HCV-related liver cirrhosis, primary liver cancer and healthy volunteers.

In this study, non-exosomal miRNAs normalized to non-exosomal-16-5p miRNAs showed a strong association with liver cancer in plasma. Three miRNAs, those with the most pronounced change in plasma expression levels – miRNA-21-5p, 122-5p, 221-3p – were detected in saliva.

Dr Alisa A. Petkevich from the Peoples’ Friendship University of Russia said: “Liver cancer, despite its relatively low incidence rate with a geographically varied global burden, is a fatal disease due to its high mortality rate: the 5-year survival rate drops from 2% to 33% depending on the stage of the disease at the time of diagnosis. “

Hepatocellular carcinoma is the most common type of primary liver cancer, affecting 80-90% of all primary liver cancers. In 20% of cases, it is an unexpected disease that develops without cirrhosis of the liver. Regardless, despite the relatively low incidence rate of malignancy in HCV-related cirrhosis and the era of direct antivirals, there is an accumulated pool of patients with HCV-related liver cirrhosis who are a. group at risk of developing liver cancer. Granted, in these cases liver cancer isn’t really an unexpected disease, but it can be clinically silent during the early stages of the disease anyway. Therefore, methods of identifying molecular changes developing in the preclinical stages of the disease are essential.

Microvesicles can contain various proteins, DNA and various RNAs including miRNA, a small non-coding nucleic acid of 18 to 24 nucleotides involved in the epigenetic regulation of gene expression. Exosomes as well as other microvesicles can serve as a target delivery system and mechanism to preserve the structure of molecules being their defense against different enzymes.

The Petkevich research team concluded in their Oncotarget research result, “remembering that primary liver cancer is highly dependent on geography, its incidence rate is relatively low in the Russian Federation [3]. This relatively low incidence rate along with other factors, including the reluctance of patients in the at-risk group to systematically go to the research center for blood collection of no personal interest, make the formation of the database of prospective cases a problem in the Russian Federation. Considering that the Liver Research Center at RUDN Medical Institute has a database of patients with HCV associated cirrhosis with contact details, a possible solution to this problem could be the use of a biomaterial that does not require the presence of medical personnel. for its collection, for example, as a saliva. In our research, we have proven that saliva is a promising approach as a source of exosomal and non-exosomal miRNA. Exosomal miRNAs normalized to exosomal-16-5p miRNA appear to be the normalizing form of miRNAs, which gives the strongest association with primary liver cancer in saliva samples. “

Reference: Petkevich AA, Abramov AA, Pospelov VI, et al. Exosomal and non-exosomal miRNA expression levels in patients with HCV-related cirrhosis and liver cancer. Oncotarget. 2021; 12 (17): 1697-1706. doi: 10.18632 / oncotarget.28036

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