statement and 2009;29(2):385–402. AJR Am J Roentgenol. Herein, we analysed four mRNA microarray datasets from Gene Expression Omnibus (GEO) to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues. Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Management of hepatocellular carcinoma. The most important module in the PPI network was identified by MCODE. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Invasion of the portal vein by a tumor has major consequences for the long-term outcome of liver transplantation for HCC. Genes were screened using the GEO (http://www.ncbi.nlm.nih.gov/geo) database, specifically the GSE89377 series on the GPL6947 platform (Illumina HumanHT12 V3.0 expression beadchip), the GSE17548 series [8] on the GPL570 platform (Affymetrix Human Genome U133 Plus 2.0 Array), the GSE63898 series [9] on the GPL13667 platform (Affymetrix Human Genome U219 Array), and the GSE54236 series [10] on the GPL6480 platform (Agilent-014850 Whole Human Genome Microarray 4x44K G4112F), the basic clinical info of the patients selected is showed in Additional file 1: Table S1. Pittsburgh, PA 15213 Any blood clots in the major branches of the portal and hepatic veins. These results suggest that CDKN3 may be a key gene in the transformation of liver cirrhosis to liver cancer, and is closely related to the occurrence and development of HCC. cBioPortal was used to identify genes closely related to changes in CDKN3, and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway) analysis was used to analyse the mechanism by which CDKN3 may affect the occurrence and development of HCC. Subsequently, protein–protein interaction (PPI) network analysis was carried out to explore relationships between different genes, hub genes were screened using the MCODE plug-in, and relationships between hub genes and prognosis were analysed by Kaplan–Meier Plotter. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Manthei KA, Yang SM, Baljinnyam B, Chang L, Glukhova A, Yuan W, et al. Lancet. 5). In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Hou J, Aerts J, den Hamer B, van IJcken W, den Bakker M, Riegman P, van der Leest C, van der Spek P, Foekens JA, Hoogsteden HC, Grosveld F, Philipsen S. Gene expression-based classification of non-small cell lung carcinomas and survival prediction. Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, 832002, China, Chen Hao Jiang, Xin Yuan, Jiang Fen Li, Yu Fang Xie, An Zhi Zhang, Xue Li Wang, Lan Yang, Chun Xia Liu, Wei Hua Liang, Li Juan Pang, Hong Zou, Xiao Bin Cui, Xi Hua Shen, Yan Qi, Jin Fang Jiang, Feng Li & Jian Ming Hu, Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Xinjiang, 832002, China, Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China, Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, 4072, Australia, You can also search for this author in CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. J Diabetes Investig. CHJ and JMH designed the study. Learn how we’re making our facilities safer and schedule your care now. According to statistical data from the International Centre for Cancer Research [21], the global incidence of HCC has increased more than 626,000 per year, and the fatality rate has reached nearly 600,000 per year. Kadalayil L, Benini R, Pallan L, O'Beirne J, Marelli L, Yu D, et al. CAS  2015;10(9):e0137397. We perform this technique, whenever possible, to reduce: If your tumor is too large to be removed by surgery, the UPMC Liver Cancer Center offers innovative therapies — such as radiofrequency ablation, transarterial chemoembolization, and yttrium-90 — to: A liver transplant may be the best option if you have HCC with cirrhosis. STRING database screening and PPI network construction were performed, and visualization was carried out using Cytoscape software (Fig. YFX, JMH,and CHJ performed statistical analyses. However, the mechanism by which cirrhosis develops into liver cancer is still unclear. Conditions or diseases associated with HCC include: Approximately 30 percent of people with HCC show no evidence of an associated condition or disease. volume 18, Article number: 40 (2020) Hepatocellular carcinoma vs. normal tissues (Wurmbach [17]); 3. Deng M, Wang J, Chen Y, Zhang L, Xie G, Liu Q, et al. Hepatology. Depending on the size and location of your tumor and the general health of your liver, you may be a candidate for surgical removal of the tumor(s). MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study. Basic Clin Pharmacol Toxicol. Insights into molecular mechanisms of drug metabolism dysfunction of human CYP2C9*30. Nucleic Acids Res. Comparative analysis of hepatocellular carcinoma and cirrhosis gene expression profiles. Shan S, Chen W, Jia JD. Part of Springer Nature. 2009;50(3):791–8. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Among them, CDKN3 plays a key role in promoting cancer by affecting the cell cycle, which is closely related to the occurrence and development of HCC. PloS ONE. © 2020 Springer Nature Switzerland AG. Wang H, Chen H, Zhou H, Yu W, Lu Z. Cyclin-dependent kinase inhibitor 3 promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p27. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. In many liver diseases, there is a significant difference in the incidence of liver cancer between the cirrhotic state and the non-cirrhotic state. To schedule an appointment, or for more information, call the UPMC Liver Cancer Center, toll-free, at 1-855-745-4837 or complete our contact form now. https://doi.org/10.1016/j.jhep.2018.03.019, https://doi.org/10.1007/978-3-319-92216-4_6. Relationships between CDKN3, CYP2C9 and LCAT, and their expression in different types of liver tissues. Am J Pathol 2003;162(2):521–31. Survival-related hub genes were analysed using the Kaplan–Meier curve feature within the Kaplan–Meier Plotter database which included 364 cases of hepatocellular carcinoma (Fig. et al. Overall survival related to hub genes was analysed using the Kaplan–Meier curve feature of Kaplan–Meier Plotter which includes 364 patients [17]. Cytoscape: a software environment for integrated models of biomolecular interaction networks. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. We noted that HCC patients with elevated CDKN3 levels were associated with a decrease in overall survival (p < 0.05) (Fig. Blood tests also help doctors determine your general health and how well your liver works, including whether you have been exposed, in the past, to hepatitis B or hepatitis C, and whether the hepatitis is active. Herein, a comprehensive Gt score > 0.4 was considered statistically significant. CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC. Genes without a corresponding gene symbol, and genes with more than one probe set are separately removed, and fold change (FC) > 2 and adjusted p < 0.05 are the threshold criteria for statistical significance. Manage cookies/Do not sell my data we use in the preference centre. Botta F, Giannini E, Romagnoli P, Fasoli A, Malfatti F, Chiarbonello B, et al. Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene. 2008;359(4):378–90. Sorafenib in advanced hepatocellular carcinoma. pp 67-82 | 2011;53(3):1020–2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is the fifth most common malignant tumour worldwide, and the second deadliest [1]. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Google Scholar. Learn more about our Centers -- from Energy and Consumer Arts & Sciences to Business and Manufacturing -- and partner with us today. 1996;201(2):353–8. Subramaniam S, Kelley RK, Venook AP. 2012;379(9822):1245–55. Rehem RN, El-Shikh WM. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. PloS ONE. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. 2011;44(3):291–9. Oncol Res. DEGs closely related to core genes were further screened by cBioPortal [18], and KEGG pathway analysis of genes related to DEGs was performed using DAVID [19]. HCC in the Community Centers of Excellence. The online database the Wurmbach liver dataset [15] which comes from Oncomine (http://www.oncomine.com) [16] was used to analyse expression levels of key genes under normal, cirrhotic, hepatocellular and hepatocyte dysplasia conditions. Not logged in PubMed Central  Horwich Cohen Coghlan. Combined with ONCOMINE database analysis, CDKN3 was identified as a key hub gene closely correlated with the progression of HCC. Aliment Pharmacol Ther. 5). String and Cytoscape were used to analyse modules and identify hub genes, Kaplan–Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Hepatology. 2017;121(4):239–45. 2015;113(12):1735–43. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. Over 10 million scientific documents at your fingertips. Villanueva A, Hoshida Y, Battiston C, Tovar V, Sia D, Alsinet C, et al. Science and Technology Development Project of Xinjiang Production and Construction Corps (NO. Once diagnosed there are several staging systems, for both the cancer and underlying liver disease, with the BCLC system being recommended in international guidelines. Biomed Pharmacother. According to the annotation information in each platform, probes were converted into corresponding gene symbols. The resulting pathway map was drawn using KEGG [20]. CAS  California Privacy Statement, PLoS One 2010;5(4):e10312. 2e–f). Holyoke Community College is a two-year college located in Holyoke, Massachusetts offering academic, transfer, and non-credit programs. J Transl Med 18, 40 (2020). Therefore, the specific regulatory mechanism by which CDKN3 influences the cell cycle remains unknown. Fold changes of the differentially expressed genes shared in GSE54236, GSE89377, GSE17548 and GSE63898. In those with indeterminate nodules on imaging criteria or with non-cirrhotic livers, a tissue diagnosis (biopsy) is needed to establish the diagnosis. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. 2007;45(4):938–47. Niculescu MD, Yamamuro Y, Zeisel SH. A review of hepatocellular carcinoma (HCC) staging systems. PubMed  PubMed Google Scholar. YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway. Not affiliated 2013;57(6):2261–73. TMHCC International takes a zero-tolerance approach to modern slavery and human trafficking in any form including: slavery, servitude, forced and compulsory labour and human trafficking (“Modern Slavery”). Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. Nakamura A, Osonoi T, Terauchi Y. Moreover, because CDKN3 is intimately linked to the occurrence, development and prognosis of liver cancer, it may be of value for the early diagnosis and treatment of tumours.

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