scholarly journals Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Chen Hao Jiang ◽  
Xin Yuan ◽  
Jiang Fen Li ◽  
Yu Fang Xie ◽  
An Zhi Zhang ◽  
...  
2020 ◽  
Author(s):  
Tianyu Li ◽  
Fang Ding ◽  
Huimin Yan

Abstract Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor, and one of the most common malignant cancer with poor prognosis. Liver cirrhosis is the major risk factor for HCC. The aim of this study was to identify potential key genes associated with the development from liver cirrhosis to HCC and explore their potential mechanisms. Methods: Four microarray datasets GSE17548, GSE63898, GSE25097 and GSE89377 were downloaded from the Gene Expression Omnibus database. A protein-protein interaction (PPI) network was constructed using the STRING database, and potential hub genes were screened using MCODE plug-in in Cytoscape software. The Oncomine database was used to verify the expression of differential genes in cirrhosis and HCC. In order to further verify those hub genes, the hierarchical cluster between normal and HCC tissues was constructed using the UCSC Cancer Genomics Browser. The UALCAN database was used to verify the difference of hub genes in normal and HCC tissues and in different tumor grades. Finally, the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC.Results: A total of 360 DEGs, including 280 downregulated and 80 upregulated genes, were identified. Gene ontology enrichment (GO) analysis showed that these DEGs were mainly enriched in monooxygenase activity, cofactor binding, and oxidoreductase activity (acting on CH-OH group of donors). The mainly enriched pathways were complement and coagulation cascades, prion diseases, and arachidonic acid metabolism. By extracting key modules from the PPI network, 16 hub genes were screened out. In the hierarchical cluster of hub genes between normal and HCC tissues, the results showed that the expression level of 16 hub genes in HCC tissues was significantly higher than that in normal tissues. In addition, expression level of the hub genes was significantly associated with the tumor grades. The survival analysis showed that six hub DEGs, including KIF20A,HMMR, RRM2, TPX2, TTK and UBE2C, were closely associated with the poor prognosis of HCC.Conclusion: Our study discovered six novel potential genes associated with the development from liver cirrhosis to HCC. These key genes may be used as prognostic biomarkers and molecular therapeutic targets for HCC.


2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.


Author(s):  
Badrinathan Sridharan ◽  
Naveen Devarajan ◽  
Rupal Jobanputra ◽  
Genekehal Siddaramana Gowd ◽  
Ida Mulayirikkal Anna ◽  
...  

2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Young-Sun Lee ◽  
Eunjung Ko ◽  
Eileen L. Yoon ◽  
Young Kul Jung ◽  
Ji Hoon Kim ◽  
...  

Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.


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