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<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">OTD</journal-id><journal-title-group><journal-title>Oncology Treatment Discovery</journal-title></journal-title-group><issn>3083-4996</issn><eissn>2981-8079</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/otd.v2i4.7956</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Comprehensive Bioinformatics Evaluation of CTNNB1 as a Diagnostic, Therapeutic and Prognostic Biomarker in Liver Hepatocellular Carcinoma</title><url>https://artdesignp.com/journal/OTD/2/4/10.26689/otd.v2i4.7956</url><author>RazaSyed Hussain,AkramMuhammad</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>2</volume><issue>4</issue><history><date date-type="pub"><published-time>2024-12-31</published-time></date></history><abstract>Liver Hepatocellular Cancer (LIHC) is a fatal disease, that keeps rigorous to therapeutic approach. This study explores the expression and promoter methylation of CTNNB1 and survival analysis, to extricate its role in LIHC progression, prognosis, and therapeutic approaches. Employing UALCAN, the study examined upregulation in CTNNB1 expression in LIHC as compared to normal samples explained its role in LIHC progression. Further analysis, stratified by patient’s age, gender, race, and pathological stages, revealed upregulation across all variables. Analysis of promoter methylation level of CTNNB1 in LIHC revealed hypomethylation, acknowledging upregulation of expression. Moreover, survival analysis of CTNNB1 using a KM plotter demonstrated its prognostic significance, as CTNNB1 overexpression results in the worst overall survival (OS) and vice versa. Validation via GEPIA2 affirmed elevated expression level of CTNNB1 in LIHC, further establishing its correlation with unfavorable survival outcomes. Furthermore, pathway enrichment analysis utilizing the STRING and DAVID tool identified association with genes implicated in essential signaling processes such as the Wnt signaling pathway revealing its role in LIHC progression. Subsequently, Genetic mutation analysis performed using cBioPortal demonstrated a 10% mutation of CTNNB1 in LIHC, indicating that alteration in the gene has a critical role in the development of LIHC. In conclusion, this comprehensive analysis highlights the significance of CTNNB1 upregulation in LIHC progression and its capability as a prognostic biomarker, offering valuable insight for developing targeted therapeutic strategies.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3): 209–249.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Tao S, Ye X, Pan L, et al., 2021, Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types. Frontiers in Genetics, 12: 784775.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Andre F, Mardis E, Salm M, et al., 2014, Prioritizing Targets for Precision Cancer Medicine. Annals of Oncology, 25(12): 2295–2303.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Sial N, Saeed S, Ahmad M, et al., 2021, Multi-Omics Analysis Identified TMED2 as a Shared Potential Biomarker in Six Subtypes of Human Cancer. International Journal of General Medicine, 2021: 7025–7042.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Anwanwan D, Singh SK, Singh S, et al., 2020, Challenges in Liver Cancer and Possible Treatment Approaches. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1873(1): 188314.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68(6): 394–424.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Balogh J, Victor III D, Asham EH, et al., 2016, Hepatocellular Carcinoma: A Review. Journal of Hepatocellular Carcinoma, 2016: 41–53.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Llovet JM, Castet F, Heikenwalder M, et al., 2022, Immunotherapies for Hepatocellular Carcinoma. Nature Reviews Clinical Oncology, 19(3): 151–172.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Park JW, Chen M, Colombo M, et al., 2015, Global Patterns of Hepatocellular Carcinoma Management from Diagnosis to Death: The BRIDGE Study. Liver International, 35(9): 2155–2166.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Heimbach JK, Kulik LM, Finn RS, et al., 2018, AASLD Guidelines for the Treatment of Hepatocellular Carcinoma. Hepatology, 67(1): 358–380.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Liu CY, Chen KF, Chen PJ, 2015, Treatment of Liver Cancer. Cold Spring Harbor Perspectives in Medicine, 5(9): a021535.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Finn RS, Qin S, Ikeda M, et al., 2020, Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma. New England Journal of Medicine, 382(20): 1894–1905.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Dhir M, Melin AA, Douaiher J, et al., 2016, A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma. Annals of Surgery, 263(6): 1112–1125.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Poon D, Anderson BO, Chen LT, et al., 2009, Management of Hepatocellular Carcinoma in Asia: Consensus Statement from the Asian Oncology Summit 2009. The Lancet Oncology, 10(11): 1111–1118.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Ouyang X, Fan Q, Ling G, et al., 2020, Identification of Diagnostic Biomarkers and Subtypes of Liver Hepatocellular Carcinoma by Multi-Omics Data Analysis. Genes (Basel), 11(9): 1051.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Kaur H, Bhalla S, Raghava GPS, 2019, Classification of Early and Late Stage Liver Hepatocellular Carcinoma Patients from Their Genomics and Epigenomics Profiles. PLoS One, 14(9): e0221476.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Huang A, Yang XR, Chung WY, et al., 2020, Targeted Therapy for Hepatocellular Carcinoma. Signal Transduction and Targeted Therapy, 5(1): 146.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Zhang W, Yang C, Hu Y, et al., 2023, Comprehensive Analysis of the Correlation of the Pan-Cancer Gene HAUS5 with Prognosis and Immune Infiltration in Liver Cancer. Scientific Reports, 13(1): 2409.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Khalaf AM, Fuentes D, Morshid AI, et al., 2018, Role of Wnt/β-Catenin Signaling in Hepatocellular Carcinoma, Pathogenesis, and Clinical Significance. Journal of Hepatocellular Carcinoma, 2018: 61–73.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Li QM, Zhang FQ, Li YF, et al., 2017, Influence of Polymorphisms in the Wnt/β-Catenin Pathway Genes on Hepatocellular Carcinoma Risk in a Chinese Han Population. Medicine, 96(12): e6127.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Pez F, Lopez A, Kim M, et al., 2013, Wnt Signaling and Hepatocarcinogenesis: Molecular Targets for the Development of Innovative Anticancer Drugs. Journal of Hepatology, 59(5): 1107–1117.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Chen L, Zhou Q, Liu J, et al., 2021, CTNNB1 Alteration is a Potential Biomarker for Immunotherapy Prognosis in Patients with Hepatocellular Carcinoma. Frontiers in Immunology, 12: 759565.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Xu C, Xu Z, Zhang Y, et al., 2022, β-Catenin Signaling in Hepatocellular Carcinoma. The Journal of Clinical Investigation, 132(4): e154515.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Chen J, Liu J, Jin R, et al., 2014, Cytoplasmic and/or Nuclear Expression of β-Catenin Correlate with Poor Prognosis and Unfavorable Clinicopathological Factors in Hepatocellular Carcinoma: A Meta-Analysis. PLoS One, 9(11): e111885.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Kim M, Lee HC, Tsedensodnom O, et al., 2008, Functional Interaction Between Wnt3 and Frizzled-7 Leads to Activation of the Wnt/β-Catenin Signaling Pathway in Hepatocellular Carcinoma Cells. Journal of Hepatology, 48(5): 780–791.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Cui J, Zhou X, Liu Y, et al., 2003, Wnt Signaling in Hepatocellular Carcinoma: Analysis of Mutation and Expression of Beta‐Catenin, T‐Cell Factor‐4 and Glycogen Synthase Kinase 3‐Beta Genes. Journal of Gastroenterology and Hepatology, 18(3): 280–287.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>MacDonald BT, Tamai K, He X, 2009, Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases. Developmental Cell, 17(1): 9–26.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Javanmard D, Najafi M, Babaei MR, et al., 2020, Investigation of CTNNB1 Gene Mutations and Expression in Hepatocellular Carcinoma and Cirrhosis in Association with Hepatitis B Virus Infection. Infectious Agents and Cancer, 15: 37.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Tornesello ML, Buonaguro L, Tatangelo F, et al., 2013, Mutations in TP53, CTNNB1 and PIK3CA Genes in Hepatocellular Carcinoma Associated with Hepatitis B and Hepatitis C Virus Infections. Genomics, 102(2): 74–83.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Saitta C, Lanza M, Bertuccio A, et al., 2015, Evaluation of CTNNB1 and TP53 Variability in Patients with Hepatocellular Carcinoma and Occult Hepatitis B Virus Infection. Cancer Genetics, 208(10): 513–516.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Chen SP, Wu CC, Huang SY, et al., 2012, β-Catenin and K-ras Mutations and RASSF1A Promoter Methylation in Taiwanese Colorectal Cancer Patients. Genetic Testing and Molecular Biomarkers, 16(11): 1277–1281.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Nusse R, Clevers H, 2017, Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell, 169(6): 985–999.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>Chandrashekar DS, Bashel B, Balasubramanya SAH, et al., 2017, UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8): 649–658.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Győrffy B, Surowiak P, Budczies J, et al., 2013, Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer. PLoS One, 8(12): e82241.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Tang Z, Kang B, Li C, et al., 2019, GEPIA2: An Enhanced Web Server for Large-Scale Expression Profiling and Interactive Analysis. Nucleic Acids Research, 47(W1): W556–W560.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Mering C, Huynen M, Jaeggi D, et al., 2003, STRING: A Database of Predicted Functional Associations Between Proteins. Nucleic Acids Research, 31(1): 258–261.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Shannon P, Markiel A, Ozier O, et al., 2003, Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research, 13(11): 2498–2504.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Da M, Zhuang J, Zhou Y, et al., 2021, Role of Long Noncoding RNA Taurine‐Upregulated Gene 1 in Cancers. Molecular Medicine, 27(1): 51.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Asakawa M, Itoh M, Suganami T, et al., 2019, Upregulation of Cancer-Associated Gene Expression in Activated Fibroblasts in a Mouse Model of Non-Alcoholic Steatohepatitis. Scientific Reports, 9(1): 19601.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B40" content-type="article"><label>40</label><element-citation publication-type="journal"><p>Anastasiadi D, Esteve-Codina A, Piferrer F, 2018, Consistent Inverse Correlation Between DNA Methylation of the First Intron and Gene Expression Across Tissues and Species. Epigenetics &amp; Chromatin, 11(1): 37.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B41" content-type="article"><label>41</label><element-citation publication-type="journal"><p>Razin A, Cedar H, 1991, DNA Methylation and Gene Expression. Microbiological Reviews, 55(3): 451–458.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B42" content-type="article"><label>42</label><element-citation publication-type="journal"><p>Polverini PJ, 2002, Angiogenesis in Health and Disease: Insights into Basic Mechanisms and Therapeutic Opportunities. Journal of Dental Education, 66(8): 962–975.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B43" content-type="article"><label>43</label><element-citation publication-type="journal"><p>Olivier M, Hollstein M, Hainaut P, 2010, TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use. Cold Spring Harbor Perspectives in Biology, 2(1): a001008.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B44" content-type="article"><label>44</label><element-citation publication-type="journal"><p>Ledinek Ž, Sobočan M, Knez J, 2022, The Role of CTNNB1 in Endometrial Cancer. Disease Markers, 2022(1): 1442441.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B45" content-type="article"><label>45</label><element-citation publication-type="journal"><p>Luczak MW, Jagodziński PP, 2006, The Role of DNA Methylation in Cancer Development. Folia Histochemica et Cytobiologica, 44(3): 143–154.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
