Prognostic utility of TME-associated genes in pancreatic cancer
Background: Pancreatic cancer (PC) is a deadly disease. The tumor microenvironment (TME) participates in PC oncogenesis. This study focuses on the assessment of the prognostic and treatment utility of TME-associated genes in PC.Methods: After obtaining the differentially expressed TME-related genes,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1218774/full |
| _version_ | 1797729265859428352 |
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| author | Yuanhua Nie Longwen Xu Zilong Bai Yaoyao Liu Shilong Wang Qingnuo Zeng Xuan Gao Xuan Gao Xuefeng Xia Dongmin Chang |
| author_facet | Yuanhua Nie Longwen Xu Zilong Bai Yaoyao Liu Shilong Wang Qingnuo Zeng Xuan Gao Xuan Gao Xuefeng Xia Dongmin Chang |
| author_sort | Yuanhua Nie |
| collection | DOAJ |
| description | Background: Pancreatic cancer (PC) is a deadly disease. The tumor microenvironment (TME) participates in PC oncogenesis. This study focuses on the assessment of the prognostic and treatment utility of TME-associated genes in PC.Methods: After obtaining the differentially expressed TME-related genes, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) were performed to identify genes related to prognosis, and a risk model was established to evaluate risk scores, based on The Cancer Genome Atlas (TCGA) data set, and it was validated by external data sets from the Gene Expression Omnibus (GEO) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Multiomics analyses were adopted to explore the potential mechanisms, discover novel treatment targets, and assess the sensitivities of immunotherapy and chemotherapy.Results: Five TME-associated genes, namely, FERMT1, CARD9, IL20RB, MET, and MMP3, were identified and a risk score formula constructed. Next, their mRNA expressions were verified in cancer and normal pancreatic cells. Multiple algorithms confirmed that the risk model displayed a reliable ability of prognosis prediction and was an independent prognostic factor, indicating that high-risk patients had poor outcomes. Immunocyte infiltration, gene set enrichment analysis (GSEA), and single-cell analysis all showed a strong relationship between immune mechanism and low-risk samples. The risk score could predict the sensitivity of immunotherapy and some chemotherapy regimens, which included oxaliplatin and irinotecan. Various latent treatment targets (LAG3, TIGIT, and ARID1A) were addressed by mutation landscape based on the risk model.Conclusion: The risk model based on TME-related genes can reflect the prognosis of PC patients and functions as a novel set of biomarkers for PC therapy. |
| first_indexed | 2024-03-12T11:26:42Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T11:26:42Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-dc1088ce9b0b498c86ebcb3dc2bfd2a82023-09-01T08:24:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12187741218774Prognostic utility of TME-associated genes in pancreatic cancerYuanhua Nie0Longwen Xu1Zilong Bai2Yaoyao Liu3Shilong Wang4Qingnuo Zeng5Xuan Gao6Xuan Gao7Xuefeng Xia8Dongmin Chang9Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaGeneplus-Beijing, Co., Ltd., Beijing, ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaGenePlus- Shenzhen Clinical Laboratory, Shenzhen, ChinaGeneplus-Beijing, Co., Ltd., Beijing, ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaBackground: Pancreatic cancer (PC) is a deadly disease. The tumor microenvironment (TME) participates in PC oncogenesis. This study focuses on the assessment of the prognostic and treatment utility of TME-associated genes in PC.Methods: After obtaining the differentially expressed TME-related genes, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) were performed to identify genes related to prognosis, and a risk model was established to evaluate risk scores, based on The Cancer Genome Atlas (TCGA) data set, and it was validated by external data sets from the Gene Expression Omnibus (GEO) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Multiomics analyses were adopted to explore the potential mechanisms, discover novel treatment targets, and assess the sensitivities of immunotherapy and chemotherapy.Results: Five TME-associated genes, namely, FERMT1, CARD9, IL20RB, MET, and MMP3, were identified and a risk score formula constructed. Next, their mRNA expressions were verified in cancer and normal pancreatic cells. Multiple algorithms confirmed that the risk model displayed a reliable ability of prognosis prediction and was an independent prognostic factor, indicating that high-risk patients had poor outcomes. Immunocyte infiltration, gene set enrichment analysis (GSEA), and single-cell analysis all showed a strong relationship between immune mechanism and low-risk samples. The risk score could predict the sensitivity of immunotherapy and some chemotherapy regimens, which included oxaliplatin and irinotecan. Various latent treatment targets (LAG3, TIGIT, and ARID1A) were addressed by mutation landscape based on the risk model.Conclusion: The risk model based on TME-related genes can reflect the prognosis of PC patients and functions as a novel set of biomarkers for PC therapy.https://www.frontiersin.org/articles/10.3389/fgene.2023.1218774/fullpancreatic cancertumor microenvironmentprognostic risk modelimmunotherapytherapeutic target |
| spellingShingle | Yuanhua Nie Longwen Xu Zilong Bai Yaoyao Liu Shilong Wang Qingnuo Zeng Xuan Gao Xuan Gao Xuefeng Xia Dongmin Chang Prognostic utility of TME-associated genes in pancreatic cancer Frontiers in Genetics pancreatic cancer tumor microenvironment prognostic risk model immunotherapy therapeutic target |
| title | Prognostic utility of TME-associated genes in pancreatic cancer |
| title_full | Prognostic utility of TME-associated genes in pancreatic cancer |
| title_fullStr | Prognostic utility of TME-associated genes in pancreatic cancer |
| title_full_unstemmed | Prognostic utility of TME-associated genes in pancreatic cancer |
| title_short | Prognostic utility of TME-associated genes in pancreatic cancer |
| title_sort | prognostic utility of tme associated genes in pancreatic cancer |
| topic | pancreatic cancer tumor microenvironment prognostic risk model immunotherapy therapeutic target |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1218774/full |
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