Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.

• Klíčová slova
• Hepatocellular carcinoma, Non-viral HCC snoRA47 and snoRD126, Prognostic marker, Small nucleolar RNA,
• Publikační typ
• časopisecké články MeSH

Hepatocellular carcinoma (HCC) is primary liver cancer, frequently diagnosed at advanced stages with limited therapeutic options. MicroRNAs (miRNAs) regulate target gene expression and through inhibitory competitive binding of miRNA influence cellular processes including carcinogenesis. Extensive evidence proved that certain miRNA's are specifically expressed in neoplastic tissues of HCC patients and are confirmed as important factors that can participate in the regulation of key signalling pathways in cancer cells. As such, miRNAs have a great potential in the clinical diagnosis and treatment of HCC and can improve the limitations of standard diagnosis and treatment. Long non-coding RNAs (lncRNAs) have a critical role in the development and progression of HCC. HCC-related lncRNAs have been demonstrated to exhibit abnormal expression and contribute to transformation process (such as proliferation, apoptosis, accelerated vascular formation, and gain of invasive potential) through their interaction with DNA, RNA, or proteins. LncRNAs can bind mRNAs to release their target mRNA and enable its translation. These lncRNA-miRNA networks regulate cancer cell expression and so its proliferation, apoptosis, invasion, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and autophagy. In this narrative review, we focus on miRNA and lncRNA in HCC tumor tissue and their interaction as current tools, and biomarkers and therapeutic targets unravelled in recent years.

• Klíčová slova
• Biomarkers, Diagnostic, Hepatocellular carcinoma, Long noncoding Ribonucleic acid, Messenger Ribonucleic acid, Micro Ribonucleic acid, Prognostic,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: We aim to estimate population-attributable fractions (PAF) for 13 comorbidities potentially predisposing to hepatobiliary cancer of hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cancers of the intrahepatic and extrahepatic bile ducts (ICC and ECC), and ampullary cancer. METHODS: Patients were identified from the Swedish Inpatient Register from 1987 to 2018 and cancers from the Swedish Cancer Registry from 1997 through 2018. PAFs were calculated for each comorbidity-associated cancer using a cohort study design. RESULTS: For male HCC, the major individual comorbidities (PAF > 10) were diabetes, alcohol-related liver disease, and hepatitis C virus infection. For female HCC, diabetes and autoimmune diseases were important contributors. For female GBC, gallstone disease was an overwhelming contributor, with a PAF of 30.57%, which was also important for men. The overall PAF for male ICC was almost two times higher than the female one. For ECC and ampullary cancer, infection of bile ducts was associated with the highest PAF. CONCLUSIONS: The 13 comorbidities accounted for 50% or more of the potential etiological pathways of each hepatobiliary cancer except female ICC. The underlying convergent mechanism for these cancers may be chronic inflammation lasting for decades and thus offering possibilities for intervention and disease monitoring.

• Klíčová slova
• alcohol, bile duct infection, comorbidity, hepatocellular carcinoma, risk factor, viral infection,
• Publikační typ
• časopisecké články MeSH