Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma
Hepatocellular carcinoma (HCC) represents the most important type of liver cancer, the 5-year survival rate for advanced HCC is 2%. The heterogeneity of HCC makes previous models fail to achieve satisfactory results. The role of Cholesterol-based metabolic reprogramming in cancer has attracted more...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022003105 |
| _version_ | 1797978193970331648 |
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| author | Linsong Tang Rongli Wei Ronggao Chen Guanghan Fan Junbin Zhou Zhetuo Qi Kai Wang Qiang Wei Xuyong Wei Xiao Xu |
| author_facet | Linsong Tang Rongli Wei Ronggao Chen Guanghan Fan Junbin Zhou Zhetuo Qi Kai Wang Qiang Wei Xuyong Wei Xiao Xu |
| author_sort | Linsong Tang |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) represents the most important type of liver cancer, the 5-year survival rate for advanced HCC is 2%. The heterogeneity of HCC makes previous models fail to achieve satisfactory results. The role of Cholesterol-based metabolic reprogramming in cancer has attracted more and more attention. In this study, we screened cholesterol metabolism-related genes (CMRGs) based on a systematical analysis from TCGA and GEO database. Then, we constructed a prognostic signature based on the screened 5 CMRGs: FDPS, FABP5, ANXA2, ACADL and HMGCS2. The clinical value of the five CMRGs was validated by TCGA database and HPA database. HCC patients were assigned to the high-risk and low-risk groups on the basis of median risk score calculated by the five CMRGs. We evaluated the signature in TCGA database and validated in ICGC database. The results revealed that the prognostic signature had good prognostic performance, even among different clinicopathological subgroups. The function analysis linked CMRGs with KEGG pathway, such as cell adhesion molecules, drug metabolism-cytochrome P450 and other related pathways. In addition, patients in the high-risk group exhibited characteristics of high TP53 mutation, high immune checkpoints expression and high immune cell infiltration. Furthermore, based on the prognostic signature, we identified 25 most significant small molecule drugs as potential drugs for HCC patients. Finally, a nomogram combined risk score and TNM stage was constructed. These results indicated our prognostic signature has an excellent prediction performance. This study is expected to provide a potential diagnostic and therapeutic strategies for HCC. |
| first_indexed | 2024-04-11T05:19:05Z |
| format | Article |
| id | doaj.art-02c866fd02fc40f3be3679d82f8f519b |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:05Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
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| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-02c866fd02fc40f3be3679d82f8f519b2022-12-24T04:53:32ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012044024414Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinomaLinsong Tang0Rongli Wei1Ronggao Chen2Guanghan Fan3Junbin Zhou4Zhetuo Qi5Kai Wang6Qiang Wei7Xuyong Wei8Xiao Xu9Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaNHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, China; Corresponding author at: Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.Hepatocellular carcinoma (HCC) represents the most important type of liver cancer, the 5-year survival rate for advanced HCC is 2%. The heterogeneity of HCC makes previous models fail to achieve satisfactory results. The role of Cholesterol-based metabolic reprogramming in cancer has attracted more and more attention. In this study, we screened cholesterol metabolism-related genes (CMRGs) based on a systematical analysis from TCGA and GEO database. Then, we constructed a prognostic signature based on the screened 5 CMRGs: FDPS, FABP5, ANXA2, ACADL and HMGCS2. The clinical value of the five CMRGs was validated by TCGA database and HPA database. HCC patients were assigned to the high-risk and low-risk groups on the basis of median risk score calculated by the five CMRGs. We evaluated the signature in TCGA database and validated in ICGC database. The results revealed that the prognostic signature had good prognostic performance, even among different clinicopathological subgroups. The function analysis linked CMRGs with KEGG pathway, such as cell adhesion molecules, drug metabolism-cytochrome P450 and other related pathways. In addition, patients in the high-risk group exhibited characteristics of high TP53 mutation, high immune checkpoints expression and high immune cell infiltration. Furthermore, based on the prognostic signature, we identified 25 most significant small molecule drugs as potential drugs for HCC patients. Finally, a nomogram combined risk score and TNM stage was constructed. These results indicated our prognostic signature has an excellent prediction performance. This study is expected to provide a potential diagnostic and therapeutic strategies for HCC.http://www.sciencedirect.com/science/article/pii/S2001037022003105Hepatocellular carcinomaCholesterol metabolismPrognostic signatureTherapeutic response |
| spellingShingle | Linsong Tang Rongli Wei Ronggao Chen Guanghan Fan Junbin Zhou Zhetuo Qi Kai Wang Qiang Wei Xuyong Wei Xiao Xu Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma Computational and Structural Biotechnology Journal Hepatocellular carcinoma Cholesterol metabolism Prognostic signature Therapeutic response |
| title | Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma |
| title_full | Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma |
| title_fullStr | Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma |
| title_full_unstemmed | Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma |
| title_short | Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma |
| title_sort | establishment and validation of a cholesterol metabolism related prognostic signature for hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Cholesterol metabolism Prognostic signature Therapeutic response |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022003105 |
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