A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer
BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic pot...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.690129/full |
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| author | Fen Liu Fen Liu Zongcheng Yang Lixin Zheng Lixin Zheng Wei Shao Wei Shao Xiujie Cui Xiujie Cui Yue Wang Yue Wang Jihui Jia Jihui Jia Yue Fu |
| author_facet | Fen Liu Fen Liu Zongcheng Yang Lixin Zheng Lixin Zheng Wei Shao Wei Shao Xiujie Cui Xiujie Cui Yue Wang Yue Wang Jihui Jia Jihui Jia Yue Fu |
| author_sort | Fen Liu |
| collection | DOAJ |
| description | BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer. |
| first_indexed | 2024-12-16T13:01:58Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T13:01:58Z |
| publishDate | 2021-06-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-ac84930042db4f8b825ef0c398a004732022-12-21T22:30:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.690129690129A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric CancerFen Liu0Fen Liu1Zongcheng Yang2Lixin Zheng3Lixin Zheng4Wei Shao5Wei Shao6Xiujie Cui7Xiujie Cui8Yue Wang9Yue Wang10Jihui Jia11Jihui Jia12Yue Fu13Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, ChinaDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, ChinaBackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.690129/fullgastric cancertumor microenvironmentimmunotherapyWGCNAprognosis |
| spellingShingle | Fen Liu Fen Liu Zongcheng Yang Lixin Zheng Lixin Zheng Wei Shao Wei Shao Xiujie Cui Xiujie Cui Yue Wang Yue Wang Jihui Jia Jihui Jia Yue Fu A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer Frontiers in Oncology gastric cancer tumor microenvironment immunotherapy WGCNA prognosis |
| title | A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer |
| title_full | A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer |
| title_fullStr | A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer |
| title_full_unstemmed | A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer |
| title_short | A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer |
| title_sort | tumor progression related 7 gene signature indicates prognosis and tumor immune characteristics of gastric cancer |
| topic | gastric cancer tumor microenvironment immunotherapy WGCNA prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.690129/full |
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