Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma
<b>Background/Objectives</b>: Hepatocellular carcinoma (HCC) remains a significant global health concern, primarily due to the limited efficacy of targeted therapies, which are often compromised by drug resistance and adverse side effects. <b>Methods</b>: In this study, we ut...
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2025-01-01
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| author | Hezhou Long Jiafu Zhou Changxia Zhou Shuyu Xie Jingling Wang Minjia Tan Junyu Xu |
| author_facet | Hezhou Long Jiafu Zhou Changxia Zhou Shuyu Xie Jingling Wang Minjia Tan Junyu Xu |
| author_sort | Hezhou Long |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Hepatocellular carcinoma (HCC) remains a significant global health concern, primarily due to the limited efficacy of targeted therapies, which are often compromised by drug resistance and adverse side effects. <b>Methods</b>: In this study, we utilized a Tandem Mass Tag (TMT)-based quantitative proteomic approach to analyze global protein expression and serine/threonine/tyrosine (S/T/Y) phosphorylation modifications in HepG2 cells following treatment with three clinically relevant hepatocellular carcinoma-targeted agents: apatinib, regorafenib, and lenvatinib. <b>Results</b>: Utilizing KEGG pathway enrichment analysis, biological process enrichment analysis, and protein interaction network analysis, we elucidated the common and specific metabolic pathways, biological processes, and protein interaction regulatory networks influenced by three liver cancer therapeutics. The study additionally proposed potential combinational treatment strategies, highlighting a possible synergistic interaction between HCC-targeted drugs and the DNA methyltransferase inhibitor. Furthermore, through the integration of clinical phosphorylation site data, we identified several phosphorylation sites that exhibited higher abundance in tumor tissues compared to adjacent non-tumor tissues. These sites were associated with poor prognosis and elevated functional scores. <b>Conclusions</b>: In summary, this study conducted an in-depth analysis of the molecular alterations in proteins and phosphorylation modifications induced by clinical HCC-targeted drugs, predicting drug combination strategies and therapeutic targets. |
| format | Article |
| id | doaj-art-1a66eb9ab391481fbf062142e4633b9e |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-1a66eb9ab391481fbf062142e4633b9e2025-01-24T13:24:12ZengMDPI AGBiomedicines2227-90592025-01-0113115210.3390/biomedicines13010152Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular CarcinomaHezhou Long0Jiafu Zhou1Changxia Zhou2Shuyu Xie3Jingling Wang4Minjia Tan5Junyu Xu6School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China<b>Background/Objectives</b>: Hepatocellular carcinoma (HCC) remains a significant global health concern, primarily due to the limited efficacy of targeted therapies, which are often compromised by drug resistance and adverse side effects. <b>Methods</b>: In this study, we utilized a Tandem Mass Tag (TMT)-based quantitative proteomic approach to analyze global protein expression and serine/threonine/tyrosine (S/T/Y) phosphorylation modifications in HepG2 cells following treatment with three clinically relevant hepatocellular carcinoma-targeted agents: apatinib, regorafenib, and lenvatinib. <b>Results</b>: Utilizing KEGG pathway enrichment analysis, biological process enrichment analysis, and protein interaction network analysis, we elucidated the common and specific metabolic pathways, biological processes, and protein interaction regulatory networks influenced by three liver cancer therapeutics. The study additionally proposed potential combinational treatment strategies, highlighting a possible synergistic interaction between HCC-targeted drugs and the DNA methyltransferase inhibitor. Furthermore, through the integration of clinical phosphorylation site data, we identified several phosphorylation sites that exhibited higher abundance in tumor tissues compared to adjacent non-tumor tissues. These sites were associated with poor prognosis and elevated functional scores. <b>Conclusions</b>: In summary, this study conducted an in-depth analysis of the molecular alterations in proteins and phosphorylation modifications induced by clinical HCC-targeted drugs, predicting drug combination strategies and therapeutic targets.https://www.mdpi.com/2227-9059/13/1/152proteomicshepatocellular carcinomahepatocellular carcinoma-targeted drugsS/T/Y phosphorylationdrug combination |
| spellingShingle | Hezhou Long Jiafu Zhou Changxia Zhou Shuyu Xie Jingling Wang Minjia Tan Junyu Xu Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma Biomedicines proteomics hepatocellular carcinoma hepatocellular carcinoma-targeted drugs S/T/Y phosphorylation drug combination |
| title | Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma |
| title_full | Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma |
| title_fullStr | Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma |
| title_full_unstemmed | Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma |
| title_short | Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma |
| title_sort | proteomic characterization of liver cancer cells treated with clinical targeted drugs for hepatocellular carcinoma |
| topic | proteomics hepatocellular carcinoma hepatocellular carcinoma-targeted drugs S/T/Y phosphorylation drug combination |
| url | https://www.mdpi.com/2227-9059/13/1/152 |
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