A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma
Zhihao Wang,1 Kidane Siele Embaye,1 Qing Yang,2 Lingzhi Qin,1 Chao Zhang,1 Liwei Liu,1 Xiaoqian Zhan,1 Fengdi Zhang,3 Xi Wang,1 Shenghui Qin1 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2021-03-01
|
| Series: | Journal of Hepatocellular Carcinoma |
| Subjects: | |
| Online Access: | https://www.dovepress.com/a-novel-metabolism-related-signature-as-a-candidate-prognostic-biomark-peer-reviewed-article-JHC |
| _version_ | 1818427180529483776 |
|---|---|
| author | Wang Z Embaye KS Yang Q Qin L Zhang C Liu L Zhan X Zhang F Wang X Qin S |
| author_facet | Wang Z Embaye KS Yang Q Qin L Zhang C Liu L Zhan X Zhang F Wang X Qin S |
| author_sort | Wang Z |
| collection | DOAJ |
| description | Zhihao Wang,1 Kidane Siele Embaye,1 Qing Yang,2 Lingzhi Qin,1 Chao Zhang,1 Liwei Liu,1 Xiaoqian Zhan,1 Fengdi Zhang,3 Xi Wang,1 Shenghui Qin1 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pharmacy, Hiser Medical Center of Qingdao, Qingdao, 266033, People’s Republic of China; 3Department of Pathology, Wuhan Third Hospital, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Shenghui QinInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-15102744765Fax + 86-027-87541509Email 2015tj0147@hust.edu.cnPurpose: Given that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes (MRGs) for the diagnosis and treatment of hepatocellular carcinoma (HCC).Methods: In total, 2752 metabolism-related gene sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). One hundred and seventy-eight the differentially expressed MRGs were identified from the ICGC cohort and TCGA cohort. Then, univariate Cox regression analysis was performed to identify these genes that were related to overall survival (OS). A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses in the ICGC dataset. The Broad Institute’s Connectivity Map (CMap) was used in predicting which compounds on the basis of the prognostic MRGs. Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in HCC cell lines by Western blotting (WB) and quantitative real-time PCR (qRT-PCR).Results: We found that 17 MRGs were most significantly associated with OS in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this particular signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Candidate drugs that aimed at hub ERGs were identified. Finally, hub genes were chosen for validation and the protein, mRNA expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human HCC cell lines compared to normal human hepatic cell lines, which were in agreement with the results of differential expression analysis.Conclusion: Our data provided evidence that the metabolism-related signature could serve as a reliable prognostic and predictive tool for OS in patients with HCC.Keywords: hepatocellular carcinoma, metabolism-related genes, prognostic signature, biomarker |
| first_indexed | 2024-12-14T14:41:38Z |
| format | Article |
| id | doaj.art-48573241b8df42988f9d6beb376d2b09 |
| institution | Directory Open Access Journal |
| issn | 2253-5969 |
| language | English |
| last_indexed | 2024-12-14T14:41:38Z |
| publishDate | 2021-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Hepatocellular Carcinoma |
| spelling | doaj.art-48573241b8df42988f9d6beb376d2b092022-12-21T22:57:24ZengDove Medical PressJournal of Hepatocellular Carcinoma2253-59692021-03-01Volume 811913263093A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular CarcinomaWang ZEmbaye KSYang QQin LZhang CLiu LZhan XZhang FWang XQin SZhihao Wang,1 Kidane Siele Embaye,1 Qing Yang,2 Lingzhi Qin,1 Chao Zhang,1 Liwei Liu,1 Xiaoqian Zhan,1 Fengdi Zhang,3 Xi Wang,1 Shenghui Qin1 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pharmacy, Hiser Medical Center of Qingdao, Qingdao, 266033, People’s Republic of China; 3Department of Pathology, Wuhan Third Hospital, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Shenghui QinInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-15102744765Fax + 86-027-87541509Email 2015tj0147@hust.edu.cnPurpose: Given that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes (MRGs) for the diagnosis and treatment of hepatocellular carcinoma (HCC).Methods: In total, 2752 metabolism-related gene sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). One hundred and seventy-eight the differentially expressed MRGs were identified from the ICGC cohort and TCGA cohort. Then, univariate Cox regression analysis was performed to identify these genes that were related to overall survival (OS). A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses in the ICGC dataset. The Broad Institute’s Connectivity Map (CMap) was used in predicting which compounds on the basis of the prognostic MRGs. Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in HCC cell lines by Western blotting (WB) and quantitative real-time PCR (qRT-PCR).Results: We found that 17 MRGs were most significantly associated with OS in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this particular signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Candidate drugs that aimed at hub ERGs were identified. Finally, hub genes were chosen for validation and the protein, mRNA expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human HCC cell lines compared to normal human hepatic cell lines, which were in agreement with the results of differential expression analysis.Conclusion: Our data provided evidence that the metabolism-related signature could serve as a reliable prognostic and predictive tool for OS in patients with HCC.Keywords: hepatocellular carcinoma, metabolism-related genes, prognostic signature, biomarkerhttps://www.dovepress.com/a-novel-metabolism-related-signature-as-a-candidate-prognostic-biomark-peer-reviewed-article-JHChepatocellular carcinomametabolism-related genesprognostic signaturebiomarker. |
| spellingShingle | Wang Z Embaye KS Yang Q Qin L Zhang C Liu L Zhan X Zhang F Wang X Qin S A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma Journal of Hepatocellular Carcinoma hepatocellular carcinoma metabolism-related genes prognostic signature biomarker. |
| title | A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma |
| title_full | A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma |
| title_fullStr | A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma |
| title_full_unstemmed | A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma |
| title_short | A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma |
| title_sort | novel metabolism related signature as a candidate prognostic biomarker for hepatocellular carcinoma |
| topic | hepatocellular carcinoma metabolism-related genes prognostic signature biomarker. |
| url | https://www.dovepress.com/a-novel-metabolism-related-signature-as-a-candidate-prognostic-biomark-peer-reviewed-article-JHC |
| work_keys_str_mv | AT wangz anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT embayeks anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT yangq anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT qinl anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhangc anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT liul anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhanx anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhangf anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT wangx anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT qins anovelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT wangz novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT embayeks novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT yangq novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT qinl novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhangc novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT liul novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhanx novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT zhangf novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT wangx novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma AT qins novelmetabolismrelatedsignatureasacandidateprognosticbiomarkerforhepatocellularcarcinoma |