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.

Bioptická Laboratoř S r o Mikulášské Nám 4 32600 Pilsen Czech Republic

Department of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 280 69120 Heidelberg Germany

Department of Integrative Medical Biology Umeå University SE 901 87 Umeå Sweden

Department of Surgery University Hospital in Pilsen and Faculty of Medicine in Pilsen Charles University Alej Svobody 80 323 00 Pilsen Czech Republic

Laboratory of Cancer Treatment and Tissue Regeneration Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 323 00 Pilsen Czech Republic

Laboratory of Translational Cancer Genomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 323 00 Pilsen Czech Republic

Sikl's Institute of Pathology Faculty of Medicine and Teaching Hospital in Pilsen Charles University Ul Dr E Beneše 13 30599 Pilsen Czech Republic

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Rumgay H., et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J. Hepatol. Dec. 2022;77(6):1598–1606. doi: 10.1016/j.jhep.2022.08.021. PubMed DOI PMC

Sung H., et al. Global cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca - Cancer J. Clin. May 2021;71(3):209–249. doi: 10.3322/caac.21660. PubMed DOI

Vogel A., Meyer T., Sapisochin G., Salem R., Saborowski A. Hepatocellular carcinoma. Lancet. Oct. 2022;400(10360):1345–1362. doi: 10.1016/S0140-6736(22)01200-4. PubMed DOI

De Benedittis C., et al. Interplay of PNPLA3 and HSD17B13 variants in modulating the risk of hepatocellular carcinoma among hepatitis C patients. Gastroenterol Res Pract. 2020;2020 doi: 10.1155/2020/4216451. PubMed DOI PMC

Smirne C., et al. Periostin circulating levels and genetic variants in patients with non-alcoholic fatty liver disease. Diagnostics. Nov. 2020;10(12) doi: 10.3390/diagnostics10121003. PubMed DOI PMC

Hemminki K., et al. Personal comorbidities and their subsequent risks for liver, gallbladder and bile duct cancers. Int. J. Cancer. Mar. 2023;152(6):1107–1114. doi: 10.1002/ijc.34308. PubMed DOI

Bruix J., Reig M., Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. Apr. 2016;150(4):835–853. doi: 10.1053/j.gastro.2015.12.041. PubMed DOI

Carissimi F., et al. Finding the seed of recurrence: hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment. World J. Gastrointest. Surg. Sep. 2021;13(9):967–978. doi: 10.4240/wjgs.v13.i9.967. PubMed DOI PMC

Liang J., et al. Non-coding small nucleolar RNA SNORD17 promotes the progression of hepatocellular carcinoma through a positive feedback loop upon p53 inactivation. Cell Death Differ. May 2022;29(5):988–1003. doi: 10.1038/s41418-022-00929-w. PubMed DOI PMC

Huang Z.-H., Du Y.-P., Wen J.-T., Lu B.-F., Zhao Y. snoRNAs: functions and mechanisms in biological processes, and roles in tumor pathophysiology. Cell Death Dis. May 2022;8(1):259. doi: 10.1038/s41420-022-01056-8. PubMed DOI PMC

Mannoor K., Liao J., Jiang F. Small nucleolar RNAs in cancer. Biochim. Biophys. Acta. Aug. 2012;1826(1):121–128. doi: 10.1016/j.bbcan.2012.03.005. PubMed DOI PMC

Okugawa Y., et al. Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. Gut. Jan. 2017;66(1):107–117. doi: 10.1136/gutjnl-2015-309359. PubMed DOI PMC

Wang G., et al. Small nucleolar RNA 42 promotes the growth of hepatocellular carcinoma through the p53 signaling pathway. Cell Death Dis. Nov. 2021;7(1):347. doi: 10.1038/s41420-021-00740-5. PubMed DOI PMC

Galardi S., Fatica A., Bachi A., Scaloni A., Presutti C., Bozzoni I. Purified box C/D snoRNPs are able to reproduce site-specific 2’-O-methylation of target RNA in vitro. Mol. Cell Biol. Oct. 2002;22(19):6663–6668. doi: 10.1128/MCB.22.19.6663-6668.2002. PubMed DOI PMC

Gao L., et al. Genome-wide small nucleolar RNA expression analysis of lung cancer by next-generation deep sequencing. Int. J. Cancer. Mar. 2015;136(6):E623–E629. doi: 10.1002/ijc.29169. PubMed DOI

Li G., et al. Small nucleolar RNA 47 promotes tumorigenesis by regulating EMT markers in hepatocellular carcinoma. Minerva Med. Oct. 2017;108(5):396–404. doi: 10.23736/S0026-4806.17.05132-1. PubMed DOI

Ding Y., et al. Identification of snoRNA SNORA71A as a novel biomarker in prognosis of hepatocellular carcinoma. Dis. Markers. Sep. 2020;2020:1–7. doi: 10.1155/2020/8879944. PubMed DOI PMC

Xu W., et al. SnoRD126 promotes the proliferation of hepatocellular carcinoma cells through transcriptional regulation of FGFR2 activation in combination with hnRNPK. Aging. Apr. 2021;13(9):13300–13317. doi: 10.18632/aging.203014. PubMed DOI PMC

Barbosa E.D.S., et al. What is the role of SNORA42 in carcinogenesis? A systematic review. Asian Pac. J. Cancer Prev. APJCP. Jul. 2023;24(7):2217–2223. doi: 10.31557/APJCP.2023.24.7.2217. PubMed DOI PMC

Shan Y., et al. SNORA42 promotes oesophageal squamous cell carcinoma development through triggering the DHX9/p65 axis. Genomics. Sep. 2021;113(5):3015–3029. doi: 10.1016/j.ygeno.2021.06.036. PubMed DOI