Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma
Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was emp...
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| Format: | Article |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-56391-w |
| _version_ | 1797259377850187776 |
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| author | Ze Wang Yuan Zhang Xiaorong Yang Tongchao Zhang Zhen Li Yang Zhong Yuan Fang Wei Chong Hao Chen Ming Lu |
| author_facet | Ze Wang Yuan Zhang Xiaorong Yang Tongchao Zhang Zhen Li Yang Zhong Yuan Fang Wei Chong Hao Chen Ming Lu |
| author_sort | Ze Wang |
| collection | DOAJ |
| description | Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients. |
| first_indexed | 2024-04-24T23:08:28Z |
| format | Article |
| id | doaj.art-c1eaf34824524fce99d1ef764dc9b68f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T23:08:28Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-c1eaf34824524fce99d1ef764dc9b68f2024-03-17T12:22:35ZengNature PortfolioScientific Reports2045-23222024-03-0114111510.1038/s41598-024-56391-wGenetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinomaZe Wang0Yuan Zhang1Xiaorong Yang2Tongchao Zhang3Zhen Li4Yang Zhong5Yuan Fang6Wei Chong7Hao Chen8Ming Lu9Clinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityDepartment of Gastrointestinal Surgery, Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical SciencesClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Clinical Research Center of Shandong University, Qilu Hospital of Shandong UniversityAbstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.https://doi.org/10.1038/s41598-024-56391-w |
| spellingShingle | Ze Wang Yuan Zhang Xiaorong Yang Tongchao Zhang Zhen Li Yang Zhong Yuan Fang Wei Chong Hao Chen Ming Lu Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma Scientific Reports |
| title | Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma |
| title_full | Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma |
| title_fullStr | Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma |
| title_full_unstemmed | Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma |
| title_short | Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma |
| title_sort | genetic and molecular characterization of metabolic pathway based clusters in esophageal squamous cell carcinoma |
| url | https://doi.org/10.1038/s41598-024-56391-w |
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