Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma
Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recen...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/2/126 |
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| author | Yusheng Chen Xuan Zou Mingjian Ma Yu Liu Ruijie Wang Zhengjie Dai Yesiboli Tashiheng Yu Yan Xianjun Yu Xu Wang Chen Liu Xuan Lin He Cheng |
| author_facet | Yusheng Chen Xuan Zou Mingjian Ma Yu Liu Ruijie Wang Zhengjie Dai Yesiboli Tashiheng Yu Yan Xianjun Yu Xu Wang Chen Liu Xuan Lin He Cheng |
| author_sort | Yusheng Chen |
| collection | DOAJ |
| description | Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (<i>DLAT</i>, <i>LIPT1</i>, <i>FDX1</i>, <i>DLD</i>, <i>PDHB</i>, <i>PDHA1</i>, and <i>LIAS</i>) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, <i>LIPT1</i>, <i>LIAS</i>, <i>DLAT</i>, <i>PDHA1</i>, and <i>DLD</i> were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC. |
| first_indexed | 2024-03-11T08:57:37Z |
| format | Article |
| id | doaj.art-15412e8925d2456381ca79daf4dea747 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-11T08:57:37Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj.art-15412e8925d2456381ca79daf4dea7472023-11-16T19:57:40ZengMDPI AGCurrent Oncology1198-00521718-77292023-01-013021648166210.3390/curroncol30020126Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal AdenocarcinomaYusheng Chen0Xuan Zou1Mingjian Ma2Yu Liu3Ruijie Wang4Zhengjie Dai5Yesiboli Tashiheng6Yu Yan7Xianjun Yu8Xu Wang9Chen Liu10Xuan Lin11He Cheng12Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaBackground: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (<i>DLAT</i>, <i>LIPT1</i>, <i>FDX1</i>, <i>DLD</i>, <i>PDHB</i>, <i>PDHA1</i>, and <i>LIAS</i>) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, <i>LIPT1</i>, <i>LIAS</i>, <i>DLAT</i>, <i>PDHA1</i>, and <i>DLD</i> were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC.https://www.mdpi.com/1718-7729/30/2/126pancreatic ductal adenocarcinomacuproptosisprognostic evaluationcell deathoverall survival |
| spellingShingle | Yusheng Chen Xuan Zou Mingjian Ma Yu Liu Ruijie Wang Zhengjie Dai Yesiboli Tashiheng Yu Yan Xianjun Yu Xu Wang Chen Liu Xuan Lin He Cheng Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma Current Oncology pancreatic ductal adenocarcinoma cuproptosis prognostic evaluation cell death overall survival |
| title | Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma |
| title_full | Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma |
| title_short | Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma |
| title_sort | expression profiles of cuproptosis related genes determine distinct subtypes of pancreatic ductal adenocarcinoma |
| topic | pancreatic ductal adenocarcinoma cuproptosis prognostic evaluation cell death overall survival |
| url | https://www.mdpi.com/1718-7729/30/2/126 |
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