Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer
Background: Gastric cancer (GC) is one of the most common malignancies worldwide, exhibiting a high morbidity, and mortality. As the various treatment methods for gastric cancer are limited by disadvantages, many efforts to improve the efficacy of these treatments are being taken. Metabolic recombin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.01778/full |
| _version_ | 1819005317282791424 |
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| author | Shanshan Yu Chuan Hu Luya Cai Xuedan Du Fan Lin Qiongjie Yu Lixiao Liu Cheng Zhang Xuan Liu Wenfeng Li Yu Zhan |
| author_facet | Shanshan Yu Chuan Hu Luya Cai Xuedan Du Fan Lin Qiongjie Yu Lixiao Liu Cheng Zhang Xuan Liu Wenfeng Li Yu Zhan |
| author_sort | Shanshan Yu |
| collection | DOAJ |
| description | Background: Gastric cancer (GC) is one of the most common malignancies worldwide, exhibiting a high morbidity, and mortality. As the various treatment methods for gastric cancer are limited by disadvantages, many efforts to improve the efficacy of these treatments are being taken. Metabolic recombination is an important characteristic of cancer and has gradually caused a recent upsurge in research. However, systematic analysis of the interaction between glycolysis and GC patient prognosis and its potential associations with immune infiltration is lacking but urgently needed.Methods: We obtained the gene expression data and clinical materials of GC derived from The Cancer Genome Atlas (TCGA) dataset. Univariate and multivariate Cox proportional regression analyses were performed to select the optimal prognosis-related genes for subsequent modeling. We then validated our data in the GEO database and further verified the gene expression using the Oncomine database and PCR experiments. Besides, Gene set variation analysis (GSVA) analysis was employed to further explore the differences in activation status of biological pathways between the high and low risk groups. Furthermore, a nomogram was adopted to predict the individualized survival rate of GC patients. Finally, a violin plot and a TIMMER analysis were performed to analyse the characteristics of immune infiltration in the microenvironment.Results: A seven-gene signature, including STC1, CLDN9, EFNA3, ZBTB7A, NT5E, NUP50, and CXCR4, was established. Based on this seven-gene signature, the patients in the training set and testing sets could be divided into high-risk and low-risk groups. In addition, a nomogram based on risk and age showed good calibration and moderate discrimination. The results proved that the seven-gene signature had a strong capacity to predict the GC patient prognosis. Collectively, the violin plot and TIMMER analysis demonstrated that an immunosuppressive tumor microenvironment caused by hyperglycolysis led to poor prognosis.Conclusion: Taken together, these results established a genetic signature for gastric cancer based on glycolysis, which has reference significance for the in-depth study of the metabolic mechanism of gastric cancer and the exploration of new clinical treatment strategies. |
| first_indexed | 2024-12-20T23:50:52Z |
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| id | doaj.art-8d0d6bc009f746c5a94af23642f95039 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T23:50:52Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8d0d6bc009f746c5a94af23642f950392022-12-21T19:22:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.01778566937Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric CancerShanshan Yu0Chuan Hu1Luya Cai2Xuedan Du3Fan Lin4Qiongjie Yu5Lixiao Liu6Cheng Zhang7Xuan Liu8Wenfeng Li9Yu Zhan10Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaBackground: Gastric cancer (GC) is one of the most common malignancies worldwide, exhibiting a high morbidity, and mortality. As the various treatment methods for gastric cancer are limited by disadvantages, many efforts to improve the efficacy of these treatments are being taken. Metabolic recombination is an important characteristic of cancer and has gradually caused a recent upsurge in research. However, systematic analysis of the interaction between glycolysis and GC patient prognosis and its potential associations with immune infiltration is lacking but urgently needed.Methods: We obtained the gene expression data and clinical materials of GC derived from The Cancer Genome Atlas (TCGA) dataset. Univariate and multivariate Cox proportional regression analyses were performed to select the optimal prognosis-related genes for subsequent modeling. We then validated our data in the GEO database and further verified the gene expression using the Oncomine database and PCR experiments. Besides, Gene set variation analysis (GSVA) analysis was employed to further explore the differences in activation status of biological pathways between the high and low risk groups. Furthermore, a nomogram was adopted to predict the individualized survival rate of GC patients. Finally, a violin plot and a TIMMER analysis were performed to analyse the characteristics of immune infiltration in the microenvironment.Results: A seven-gene signature, including STC1, CLDN9, EFNA3, ZBTB7A, NT5E, NUP50, and CXCR4, was established. Based on this seven-gene signature, the patients in the training set and testing sets could be divided into high-risk and low-risk groups. In addition, a nomogram based on risk and age showed good calibration and moderate discrimination. The results proved that the seven-gene signature had a strong capacity to predict the GC patient prognosis. Collectively, the violin plot and TIMMER analysis demonstrated that an immunosuppressive tumor microenvironment caused by hyperglycolysis led to poor prognosis.Conclusion: Taken together, these results established a genetic signature for gastric cancer based on glycolysis, which has reference significance for the in-depth study of the metabolic mechanism of gastric cancer and the exploration of new clinical treatment strategies.https://www.frontiersin.org/article/10.3389/fonc.2020.01778/fullgastric cancerglycolysisprognosticriskimmune signatures |
| spellingShingle | Shanshan Yu Chuan Hu Luya Cai Xuedan Du Fan Lin Qiongjie Yu Lixiao Liu Cheng Zhang Xuan Liu Wenfeng Li Yu Zhan Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer Frontiers in Oncology gastric cancer glycolysis prognostic risk immune signatures |
| title | Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer |
| title_full | Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer |
| title_fullStr | Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer |
| title_full_unstemmed | Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer |
| title_short | Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer |
| title_sort | seven gene signature based on glycolysis is closely related to the prognosis and tumor immune infiltration of patients with gastric cancer |
| topic | gastric cancer glycolysis prognostic risk immune signatures |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.01778/full |
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