Hepatocellular carcinoma (HCC) is the leading cause of liver transplantation and one of the most common cancers. Previous results from our laboratory point to AURKB, a protein that regulates chromosomal segregation and cytokinesis processes during mitosis, as a possible marker for the evolution of liver fibrosis and / or cirrhosis and HCC. Therefore, we are studying the role of AURKB in the development of fibrosis / cirrhosis and HCC, on a cohort of 348 patients with chronic hepatitis C that demonstrates how the presence of two AURKB SNPs is significantly associated with liver fibrosis progression and HCC outcome. One of these SNPs codified for a threonine residue that contributes to the kinase activity of AURKB, essential in the phosphorylation of P53 and the CHMP4C protein. Thus, the presence of these SNPs could contribute to the development of precancerous lesions in the liver through defects in the cell cycle progression and in the chromosomal segregation and cytokinesis.
Genetic studies performed in our laboratory by next-generation sequencing assays of cell populations in which these variants are expressed, might explain the fibrosis, cirrhosis and / or hepatocarcinoma development observed in a cohort of patients infected with the hepatitis C virus.
MICROBIOTA MODIFICATIONS IN ONCOLOGICAL PATIENTS TREATED WITH BIOLOGICAL THERAPY
One of the main goals in our laboratory is related to the effects of immunotherapy on the intestinal microbiota population. Biological therapy is a new therapy against cancer which blocks specific targets of tumor cells, among which are immune ckeckpoint blockers such as anti-PD-1 and anti-CTL4 antibodies.
These treatments increase the survival of cancer patients of different types, but show a high incidence (around 85%) of gastrointestinal side effects, primary colitis or intestinal perforations that compromise the continuity of therapy. In addition, one of the most serious processes and frequently associated with cancer is malnutrition. Recent research seems to indicate that a significant proportion of patients subjected to this type of therapy undergoes a modification in the composition of the intestinal microbiota, associated to biological therapy. The microbiota is essential for proper body growth, with essential functions such as metabolism, the regulation of immunity, as well as mediating systemic inflammation. Recent studies have shown that modifications in the intestinal microbiota could lead to chronic inflammation processes, which could be considered a predictive factor for the development of side effects at the level of digestive function. Therefore, in our laboratory we are analyzing by third generation massive sequencing the composition and evolution of the microbiota in cancer patients. These studies are focused to anticipate both the appearance of nutritional disorders that compromise adherence to treatment, and to identify the appearance of risk factors for the development of intestinal inflammation
Regarding liver cancer, in 2020, the FDA approved the use of the combination of Nivolumab and Ipilimumab in the treatment of HCC patients previously treated with sorafenib. We are analyzing the effect of biological therapy on the composition of the microbiota, but also how the variation of populations affects the progression of liver disease. The phenomenon of bacterial translocation suffered by patients with liver cirrhosis related to bacterial overgrowth is of special relevance. A comprehensive study of alterations in the intestinal microbiota and their effect on the host's immune response can contribute to the design of innovative strategies for the treatment of chronic liver disease including HCC.