Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
BackgroundThe relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear.MethodsBas...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1153353/full |
| _version_ | 1797858971658223616 |
|---|---|
| author | Wei Yuan Jun-hao Xiao Jian-song Zhang Ben-liang Mao Peng-zhen Wang Bai-lin Wang |
| author_facet | Wei Yuan Jun-hao Xiao Jian-song Zhang Ben-liang Mao Peng-zhen Wang Bai-lin Wang |
| author_sort | Wei Yuan |
| collection | DOAJ |
| description | BackgroundThe relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear.MethodsBased on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed.ResultsWe constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks.ConclusionsWe constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy. |
| first_indexed | 2024-04-09T21:22:02Z |
| format | Article |
| id | doaj.art-c60e502c4aec4bbb99fac794961bceab |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T21:22:02Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c60e502c4aec4bbb99fac794961bceab2023-03-28T05:08:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.11533531153353Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinomaWei Yuan0Jun-hao Xiao1Jian-song Zhang2Ben-liang Mao3Peng-zhen Wang4Bai-lin Wang5Department of Hepatobiliary Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Clinical medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of Clinical medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of Clinical medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaGuangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Hepatobiliary Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaBackgroundThe relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear.MethodsBased on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed.ResultsWe constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks.ConclusionsWe constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2023.1153353/fullAL590705.3LINC02870KDM4A-AS1MKLN1-AShepatocellular carcinomaimmunological characteristics |
| spellingShingle | Wei Yuan Jun-hao Xiao Jian-song Zhang Ben-liang Mao Peng-zhen Wang Bai-lin Wang Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma Frontiers in Oncology AL590705.3 LINC02870 KDM4A-AS1 MKLN1-AS hepatocellular carcinoma immunological characteristics |
| title | Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| title_full | Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| title_fullStr | Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| title_full_unstemmed | Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| title_short | Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| title_sort | identification of a cuproptosis and copper metabolism gene related lncrnas prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma |
| topic | AL590705.3 LINC02870 KDM4A-AS1 MKLN1-AS hepatocellular carcinoma immunological characteristics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1153353/full |
| work_keys_str_mv | AT weiyuan identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma AT junhaoxiao identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma AT jiansongzhang identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma AT benliangmao identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma AT pengzhenwang identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma AT bailinwang identificationofacuproptosisandcoppermetabolismgenerelatedlncrnasprognosticsignatureassociatedwithclinicalandimmunologicalcharacteristicsofhepatocellularcarcinoma |